Engineering the Tumor Immune Microenvironment

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 44976

Special Issue Editor

Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA
Interests: tumor engineering; tumor evolution; tumor microbiome; targeted cancer therapies; microfluidics; nanotechnology; biomaterials; tissue engineering

Special Issue Information

Dear Colleagues,

Cancer immunotherapies (CITs) promise to revolutionize the treatment of a host of advanced malignancies for which few, if any, treatment options currently exist. Yet, a number of critical barriers remain that limit the ultimate potential of these technologies to improve outcomes for all patients. The often highly immunosuppressive tumor immune microenvironment (TIME), high degree of tumor antigen heterogeneity, evolution of resistance to targeted immunotherapies, and physical barriers that impede molecular, as well as immune cell, transport are just a few of the hurdles that must be overcome by the next generation of CITs. We believe many of the critical solutions to these, as well as other, barriers exist at the convergence of cancer biology and immunology with approaches from engineering and the physical sciences. We invite submissions of both review papers and original research articles on topics covering the use of engineering/physical sciences approaches to enhance CITs. Proposed submission topics could include, but are not limited to, lowering barriers to transport throughout the TIME, driving an anti-tumor abscopal effect with physics-based therapies, enhancing CITs with nanotechnology and/or cellular engineering, and nano/microtechnology to design patient-specific CITs. 

Dr. Scott S Verbridge
Guest Editor

Manuscript Submission Information

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Keywords

  • cancer immunotherapies
  • engineering approaches to cancer treatment
  • patient-specific immunotherapies
  • nanotherapeutics
  • bioengineering in cancer
  • engineered t-cells
  • physics-based immunotherapies

Published Papers (14 papers)

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Editorial

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3 pages, 188 KiB  
Editorial
Editorial: ‘Engineering the Tumor Immune Microenvironment’ Special Issue
by Raffae N. Ahmad and Scott S. Verbridge
Cancers 2023, 15(16), 4014; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15164014 - 08 Aug 2023
Viewed by 804
Abstract
Cancer immunotherapies, while promising and occasionally even curative, encounter numerous hurdles within the tumor microenvironment that hinder their efficacy [...] Full article
(This article belongs to the Special Issue Engineering the Tumor Immune Microenvironment)

Research

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16 pages, 1575 KiB  
Article
5-Azacytidine-Mediated Modulation of the Immune Microenvironment in Murine Acute Myeloid Leukemia
by Nancy D. Ebelt and Edwin R. Manuel
Cancers 2023, 15(1), 118; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15010118 - 25 Dec 2022
Cited by 1 | Viewed by 2199
Abstract
Cancer cells accumulate epigenetic modifications that allow escape from intrinsic and extrinsic surveillance mechanisms. In the case of acute myeloid leukemias (AML) and myelodysplastic syndromes, agents that disrupt chromatin structure, namely hypomethylating agents (HMAs), have shown tremendous promise as an alternate, milder treatment [...] Read more.
Cancer cells accumulate epigenetic modifications that allow escape from intrinsic and extrinsic surveillance mechanisms. In the case of acute myeloid leukemias (AML) and myelodysplastic syndromes, agents that disrupt chromatin structure, namely hypomethylating agents (HMAs), have shown tremendous promise as an alternate, milder treatment option for older, clinically non-fit patients. HMAs reprogram the epigenetic landscape in tumor cells through the reversal of DNA hypermethylation. Therapeutic effects resulting from these epigenetic changes are incredibly effective, sometimes resulting in complete remissions, but are frequently lost due to primary or acquired resistance. In this study, we describe syngeneic murine leukemias that are responsive to the HMA 5-azacytidine (5-Aza), as determined by augmented expression of a transduced luciferase reporter. We also found that 5-Aza treatment re-established immune-related transcript expression, suppressed leukemic burden and extended survival in leukemia-challenged mice. The effects of 5-Aza treatment were short-lived, and analysis of the immune microenvironment reveals possible mechanisms of resistance, such as simultaneous increase in immune checkpoint protein expression. This represents a model system that is highly responsive to HMAs and recapitulates major therapeutic outcomes observed in human leukemia (relapse) and may serve as a pre-clinical tool for studying acquired resistance and novel treatment combinations. Full article
(This article belongs to the Special Issue Engineering the Tumor Immune Microenvironment)
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19 pages, 3554 KiB  
Article
Targeted Depletion of Hyaluronic Acid Mitigates Murine Breast Cancer Growth
by Vic Zamloot, Nancy Danielle Ebelt, Catherine Soo, Shweta Jinka and Edwin R. Manuel
Cancers 2022, 14(19), 4614; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14194614 - 23 Sep 2022
Cited by 3 | Viewed by 1935
Abstract
Hyaluronic acid (HA) is highly elevated in breast cancers compared to normal breast tissue and is associated with increased tumor aggressiveness and poor prognosis. HA interacts with cell-trafficking CD44 receptors to promote tumor cell migration and proliferation and regulates both pro- and anti-inflammatory [...] Read more.
Hyaluronic acid (HA) is highly elevated in breast cancers compared to normal breast tissue and is associated with increased tumor aggressiveness and poor prognosis. HA interacts with cell-trafficking CD44 receptors to promote tumor cell migration and proliferation and regulates both pro- and anti-inflammatory cytokine production through tumor-associated macrophages. The highly negative charge of HA enables its uptake of vast amounts of water that greatly increases the tumor interstitial fluidic pressure, which, combined with the presence of other extracellular matrix components such as collagen, results in tumor stroma with abnormal vasculature, hypoxia, and increased drug resistance. Thus, the degradation of HA in breast cancer may attenuate growth and improve permeability to anticancer agents. Previous methods to deplete tumor HA have resulted in significant off-tumor effects due to the systemic use of mammalian hyaluronidases. To overcome this, we developed a hyaluronidase-secreting Salmonella typhimurium (YS-HAse) that specifically and preferentially colonizes tumors to deplete HA. We show that the systemic administration of YS-HAse in immunocompetent murine models of breast cancer enhances tumor perfusion, controls tumor growth, and restructures the tumor immune contexture. These studies highlight the utility of YS-HAse as a novel microbial-based therapeutic that may also be combined with existing therapeutic approaches. Full article
(This article belongs to the Special Issue Engineering the Tumor Immune Microenvironment)
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16 pages, 2791 KiB  
Article
Temsirolimus Enhances Anti-Cancer Immunity by Inducing Autophagy-Mediated Degradation of the Secretion of Small Extracellular Vesicle PD-L1
by Seong-Sik Park, Jong-In Kim, Chan-Hyeong Lee, Ju-Hyun Bae, Ju-Mi Park, Eun-Ji Choe and Moon-Chang Baek
Cancers 2022, 14(17), 4081; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14174081 - 23 Aug 2022
Cited by 7 | Viewed by 2175
Abstract
Tumor-derived small extracellular vesicle (sEV) programmed death-ligand 1 (PD-L1) contributes to the low reactivity of cells to immune checkpoint blockade therapy (ICBT), because sEV PD-L1 binds to programmed death 1 (PD-1) in immune cells. However, there are no commercially available anti-cancer drugs that [...] Read more.
Tumor-derived small extracellular vesicle (sEV) programmed death-ligand 1 (PD-L1) contributes to the low reactivity of cells to immune checkpoint blockade therapy (ICBT), because sEV PD-L1 binds to programmed death 1 (PD-1) in immune cells. However, there are no commercially available anti-cancer drugs that activate immune cells by inhibiting tumor-derived sEV PD-L1 secretion and cellular PD-L1. Here, we aimed to investigate if temsirolimus (TEM) inhibits both sEV PD-L1 and cellular PD-L1 levels in MDA-MB-231 cells. In cancer cell autophagy activated by TEM, multivesicular bodies (MVBs) associated with the secretion of sEV are degraded through colocalization with autophagosomes or lysosomes. TEM promotes CD8+ T cell-mediated anti-cancer immunity in co-cultures of CD8+ T cells and tumor cells. Furthermore, the combination therapy of TEM and anti-PD-L1 antibodies enhanced anti-cancer immunity by increasing both the number and activity of CD4+ and CD8+ T cells in the tumor and draining lymph nodes (DLNs) of breast cancer-bearing immunocompetent mice. In contrast, the anti-cancer effect of the combination therapy with TEM and anti-PD-L1 antibodies was reversed by the injection of exogenous sEV PD-L1. These findings suggest that TEM, previously known as a targeted anti-cancer drug, can overcome the low reactivity of ICBT by inhibiting sEV PD-L1 and cellular PD-L1 levels. Full article
(This article belongs to the Special Issue Engineering the Tumor Immune Microenvironment)
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15 pages, 2703 KiB  
Article
Myeloid Derived Suppressor Cells Migrate in Response to Flow and Lymphatic Endothelial Cell Interaction in the Breast Tumor Microenvironment
by LaDeidra Monét Roberts, Matthew J. Perez, Kristen N. Balogh, Garnett Mingledorff, Janet V. Cross and Jennifer M. Munson
Cancers 2022, 14(12), 3008; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14123008 - 18 Jun 2022
Cited by 5 | Viewed by 2598
Abstract
At the site of the tumor, myeloid derived suppressor cells (MDSCs) infiltrate and interact with elements of the tumor microenvironment in complex ways. Within the invading tumor, MDSCs are exposed to interstitial fluid flow (IFF) that exists within the chronic inflammatory tumor microenvironment [...] Read more.
At the site of the tumor, myeloid derived suppressor cells (MDSCs) infiltrate and interact with elements of the tumor microenvironment in complex ways. Within the invading tumor, MDSCs are exposed to interstitial fluid flow (IFF) that exists within the chronic inflammatory tumor microenvironment at the tumor–lymphatic interface. As drivers of cell migration and invasion, the link between interstitial fluid flow, lymphatics, and MDSCs have not been clearly established. Here, we hypothesized that interstitial fluid flow and cells within the breast tumor microenvironment modulate migration of MDSCs. We developed a novel 3D model to mimic the breast tumor microenvironment and incorporated MDSCs harvested from 4T1-tumor bearing mice. Using live imaging, we found that sorted GR1+ splenocytes had reduced chemotactic index compared to the unsorted population, but their speed and displacement were similar. Using our adapted tissue culture insert assay, we show that interstitial fluid flow promotes MDSC invasion, regardless of absence or presence of tumor cells. Coordinating with lymphatic endothelial cells, interstitial fluid flow further enhanced invasion of MDSCs in the presence of 4T1 cells. We also show that VEGFR3 inhibition reduced both MDSC and 4T1 flow response. Together, these findings indicate a key role of interstitial fluid flow in MDSC migration as well as describe a tool to explore the immune microenvironment in breast cancer. Full article
(This article belongs to the Special Issue Engineering the Tumor Immune Microenvironment)
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17 pages, 3161 KiB  
Article
Targeting Immunosuppressive Tumor-Associated Macrophages Using Innate T Cells for Enhanced Antitumor Reactivity
by Yan-Ruide Li, James Brown, Yanqi Yu, Derek Lee, Kuangyi Zhou, Zachary Spencer Dunn, Ryan Hon, Matthew Wilson, Adam Kramer, Yichen Zhu, Ying Fang and Lili Yang
Cancers 2022, 14(11), 2749; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14112749 - 01 Jun 2022
Cited by 26 | Viewed by 3927
Abstract
The field of T cell-based and chimeric antigen receptor (CAR)-engineered T (CAR-T) cell-based antitumor immunotherapy has seen substantial developments in the past decade; however, considerable issues, such as graft-versus-host disease (GvHD) and tumor-associated immunosuppression, have proven to be substantial roadblocks to widespread adoption [...] Read more.
The field of T cell-based and chimeric antigen receptor (CAR)-engineered T (CAR-T) cell-based antitumor immunotherapy has seen substantial developments in the past decade; however, considerable issues, such as graft-versus-host disease (GvHD) and tumor-associated immunosuppression, have proven to be substantial roadblocks to widespread adoption and implementation. Recent developments in innate immune cell-based CAR therapy have opened several doors for the expansion of this therapy, especially as it relates to allogeneic cell sources and solid tumor infiltration. This study establishes in vitro killing assays to examine the TAM-targeting efficacy of MAIT, iNKT, and γδT cells. This study also assesses the antitumor ability of CAR-engineered innate T cells, evaluating their potential adoption for clinical therapies. The in vitro trials presented in this study demonstrate the considerable TAM-killing abilities of all three innate T cell types, and confirm the enhanced antitumor abilities of CAR-engineered innate T cells. The tumor- and TAM-targeting capacity of these innate T cells suggest their potential for antitumor therapy that supplements cytotoxicity with remediation of tumor microenvironment (TME)-immunosuppression. Full article
(This article belongs to the Special Issue Engineering the Tumor Immune Microenvironment)
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18 pages, 2344 KiB  
Article
T-Cells Expressing a Highly Potent PRAME-Specific T-Cell Receptor in Combination with a Chimeric PD1-41BB Co-Stimulatory Receptor Show a Favorable Preclinical Safety Profile and Strong Anti-Tumor Reactivity
by Nadja Sailer, Ina Fetzer, Melanie Salvermoser, Monika Braun, Doris Brechtefeld, Christian Krendl, Christiane Geiger, Kathrin Mutze, Elfriede Noessner, Dolores J. Schendel, Maja Bürdek, Susanne Wilde and Daniel Sommermeyer
Cancers 2022, 14(8), 1998; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14081998 - 14 Apr 2022
Cited by 9 | Viewed by 7201
Abstract
The hostile tumor microenvironment (TME) is a major challenge for the treatment of solid tumors with T-cell receptor (TCR)-modified T-cells (TCR-Ts), as it negatively influences T-cell efficacy, fitness, and persistence. These negative influences are caused, among others, by the inhibitory checkpoint PD-1/PD-L1 axis. [...] Read more.
The hostile tumor microenvironment (TME) is a major challenge for the treatment of solid tumors with T-cell receptor (TCR)-modified T-cells (TCR-Ts), as it negatively influences T-cell efficacy, fitness, and persistence. These negative influences are caused, among others, by the inhibitory checkpoint PD-1/PD-L1 axis. The Preferentially Expressed Antigen in Melanoma (PRAME) is a highly relevant cancer/testis antigen for TCR-T immunotherapy due to broad expression in multiple solid cancer indications. A TCR with high specificity and sensitivity for PRAME was isolated from non-tolerized T-cell repertoires and introduced into T-cells alongside a chimeric PD1-41BB receptor, consisting of the natural extracellular domain of PD-1 and the intracellular signaling domain of 4-1BB, turning an inhibitory pathway into a T-cell co-stimulatory pathway. The addition of PD1-41BB to CD8+ T-cells expressing the transgenic PRAME-TCR enhanced IFN-γ secretion, improved cytotoxic capacity, and prevented exhaustion upon repetitive re-challenge with tumor cells in vitro without altering the in vitro safety profile. Furthermore, a single dose of TCR-Ts co-expressing PD1-41BB was sufficient to clear a hard-to-treat melanoma xenograft in a mouse model, whereas TCR-Ts without PD1-41BB could not eradicate the PD-L1-positive tumors. This cutting-edge strategy supports development efforts to provide more effective TCR-T immunotherapies for the treatment of solid tumors. Full article
(This article belongs to the Special Issue Engineering the Tumor Immune Microenvironment)
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12 pages, 1689 KiB  
Communication
Minimally Invasive Preclinical Monitoring of the Peritoneal Cavity Tumor Microenvironment
by Zachary Spencer Dunn, Yan-Ruide Li, Yanqi Yu, Derek Lee, Alicia Gibbons, James Joon Kim, Tian Yang Zhou, Mulin Li, Mya Nguyen, Xinjian Cen, Yang Zhou, Pin Wang and Lili Yang
Cancers 2022, 14(7), 1775; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14071775 - 31 Mar 2022
Cited by 2 | Viewed by 2611
Abstract
Intraperitoneal (i.p.) experimental models in mice can recapitulate the process of i.p. dissemination in abdominal cancers and may help uncover critical information about future successful clinical treatments. i.p. cellular composition is studied in preclinical models addressing a wide spectrum of other pathophysiological states [...] Read more.
Intraperitoneal (i.p.) experimental models in mice can recapitulate the process of i.p. dissemination in abdominal cancers and may help uncover critical information about future successful clinical treatments. i.p. cellular composition is studied in preclinical models addressing a wide spectrum of other pathophysiological states such as liver cirrhosis, infectious disease, autoimmunity, and aging. The peritoneal cavity is a multifaceted microenvironment that contains various immune cell populations, including T, B, NK, and various myeloid cells, such as macrophages. Analysis of the peritoneal cavity is often obtained by euthanizing mice and performing terminal peritoneal lavage. This procedure inhibits continuous monitoring of the peritoneal cavity in a single mouse and necessitates the usage of more mice to assess the cavity at multiple timepoints, increasing the cost, time, and variability of i.p. studies. Here, we present a simple, novel method termed in vivo intraperitoneal lavage (IVIPL) for the minimally invasive monitoring of cells in the peritoneal cavity of mice. In this proof-of-concept, IVIPL provided real-time insights into the i.p. tumor microenvironment for the development and study of ovarian cancer therapies. Specifically, we studied CAR-T cell therapy in a human high-grade serous ovarian cancer (HGSOC) xenograft mouse model, and we studied the immune composition of the i.p. tumor microenvironment (TME) in a mouse HGSOC syngeneic model. Full article
(This article belongs to the Special Issue Engineering the Tumor Immune Microenvironment)
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Review

Jump to: Editorial, Research, Other

33 pages, 2417 KiB  
Review
Paving the Way to Solid Tumors: Challenges and Strategies for Adoptively Transferred Transgenic T Cells in the Tumor Microenvironment
by Franziska Füchsl and Angela M. Krackhardt
Cancers 2022, 14(17), 4192; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14174192 - 29 Aug 2022
Cited by 6 | Viewed by 3272
Abstract
T cells are important players in the antitumor immune response. Over the past few years, the adoptive transfer of genetically modified, autologous T cells—specifically redirected toward the tumor by expressing either a T cell receptor (TCR) or a chimeric antigen receptor (CAR)—has been [...] Read more.
T cells are important players in the antitumor immune response. Over the past few years, the adoptive transfer of genetically modified, autologous T cells—specifically redirected toward the tumor by expressing either a T cell receptor (TCR) or a chimeric antigen receptor (CAR)—has been adopted for use in the clinic. At the moment, the therapeutic application of CD19- and, increasingly, BCMA-targeting-engineered CAR-T cells have been approved and have yielded partly impressive results in hematologic malignancies. However, employing transgenic T cells for the treatment of solid tumors remains more troublesome, and numerous hurdles within the highly immunosuppressive tumor microenvironment (TME) need to be overcome to achieve tumor control. In this review, we focused on the challenges that these therapies must face on three different levels: infiltrating the tumor, exerting efficient antitumor activity, and overcoming T cell exhaustion and dysfunction. We aimed to discuss different options to pave the way for potent transgenic T cell-mediated tumor rejection by engineering either the TME or the transgenic T cell itself, which responds to the environment. Full article
(This article belongs to the Special Issue Engineering the Tumor Immune Microenvironment)
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16 pages, 935 KiB  
Review
Local Breast Microbiota: A “New” Player on the Block
by Marina Vitorino, Diogo Alpuim Costa, Rodrigo Vicente, Telma Caleça and Catarina Santos
Cancers 2022, 14(15), 3811; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14153811 - 05 Aug 2022
Cited by 14 | Viewed by 5290
Abstract
The tumour microenvironment (TME) comprises a complex ecosystem of different cell types, including immune cells, cells of the vasculature and lymphatic system, cancer-associated fibroblasts, pericytes, and adipocytes. Cancer proliferation, invasion, metastasis, drug resistance and immune escape are all influenced by the dynamic interaction [...] Read more.
The tumour microenvironment (TME) comprises a complex ecosystem of different cell types, including immune cells, cells of the vasculature and lymphatic system, cancer-associated fibroblasts, pericytes, and adipocytes. Cancer proliferation, invasion, metastasis, drug resistance and immune escape are all influenced by the dynamic interaction between cancer cells and TME. Microbes, such as bacteria, fungi, viruses, archaea and protists, found within tumour tissues, constitute the intratumour microbiota, which is tumour type-specific and distinct among patients with different clinical outcomes. Growing evidence reveals a significant relevance of local microbiota in the colon, liver, breast, lung, oral cavity and pancreas carcinogenesis. Moreover, there is a growing interest in the tumour immune microenvironment (TIME) pointed out in several cross-sectional studies on the correlation between microbiota and TME. It is now known that microorganisms have the capacity to change the density and function of anticancer and suppressive immune cells, enabling the promotion of an inflammatory environment. As immunotherapy (such as immune checkpoint inhibitors) is becoming a promising therapy using TIME as a therapeutic target, the analysis and comprehension of local microbiota and its modulating strategies can help improve cancer treatments. Full article
(This article belongs to the Special Issue Engineering the Tumor Immune Microenvironment)
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11 pages, 1583 KiB  
Review
Tertiary Lymphoid Structures as Mediators of Immunotherapy Response
by Raj G. Vaghjiani and Joseph J. Skitzki
Cancers 2022, 14(15), 3748; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14153748 - 01 Aug 2022
Cited by 13 | Viewed by 4565
Abstract
Since its first application in the treatment of cancer during the 1800s, immunotherapy has more recently become the leading edge of novel treatment strategies. Even though the efficacy of these agents can at times be predicted by more traditional metrics and biomarkers, often [...] Read more.
Since its first application in the treatment of cancer during the 1800s, immunotherapy has more recently become the leading edge of novel treatment strategies. Even though the efficacy of these agents can at times be predicted by more traditional metrics and biomarkers, often patient responses are variable. TLS are distinct immunologic structures that have been identified on pathologic review of various malignancies and are emerging as important determinants of patient outcome. Their presence, location, composition, and maturity are critically important in a host’s response to malignancy. Because of their unique immunogenic niche, they are also prime candidates, not only to predict and measure the efficacy of immunotherapy agents, but also to be potentially inducible gatekeepers to increase therapeutic efficacy. Herein, we review the mechanistic underpinnings of TLS formation, the data on its relationship to various malignancies, and the emerging evidence for the role of TLS in immunotherapy function. Full article
(This article belongs to the Special Issue Engineering the Tumor Immune Microenvironment)
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14 pages, 731 KiB  
Review
The Route of the Malignant Plasma Cell in Its Survival Niche: Exploring “Multiple Myelomas”
by Antonio Giovanni Solimando, Matteo Claudio Da Vià, Niccolò Bolli and Torsten Steinbrunn
Cancers 2022, 14(13), 3271; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14133271 - 04 Jul 2022
Cited by 5 | Viewed by 2465
Abstract
Growing evidence points to multiple myeloma (MM) and its stromal microenvironment using several mechanisms to subvert effective immune and anti-tumor responses. Recent advances have uncovered the tumor-stromal cell influence in regulating the immune-microenvironment and have envisioned targeting these suppressive pathways to improve therapeutic [...] Read more.
Growing evidence points to multiple myeloma (MM) and its stromal microenvironment using several mechanisms to subvert effective immune and anti-tumor responses. Recent advances have uncovered the tumor-stromal cell influence in regulating the immune-microenvironment and have envisioned targeting these suppressive pathways to improve therapeutic outcomes. Nevertheless, some subgroups of patients include those with particularly unfavorable prognoses. Biological stratification can be used to categorize patient-, disease- or therapy-related factors, or alternatively, these biological determinants can be included in a dynamic model that customizes a given treatment to a specific patient. Genetic heterogeneity and current knowledge enforce a systematic and comprehensive bench-to-bedside approach. Given the increasing role of cancer stem cells (CSCs) in better characterizing the pathogenesis of solid and hematological malignancies, disease relapse, and drug resistance, identifying and describing CSCs is of paramount importance in the management of MM. Even though the function of CSCs is well-known in other cancer types, their role in MM remains elusive. With this review, we aim to provide an update on MM homing and resilience in the bone marrow micro milieu. These data are particularly interesting for clinicians facing unmet medical needs while designing novel treatment approaches for MM. Full article
(This article belongs to the Special Issue Engineering the Tumor Immune Microenvironment)
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16 pages, 880 KiB  
Review
Dialogue among Lymphocytes and Microglia in Glioblastoma Microenvironment
by Alessandro Mormino and Stefano Garofalo
Cancers 2022, 14(11), 2632; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14112632 - 26 May 2022
Cited by 3 | Viewed by 2379
Abstract
Microglia and lymphocytes are fundamental constituents of the glioblastoma microenvironment. In this review, we summarize the current state-of-the-art knowledge of the microglial role played in promoting the development and aggressive hallmarks of this deadly brain tumor. Particularly, we report in vitro and in [...] Read more.
Microglia and lymphocytes are fundamental constituents of the glioblastoma microenvironment. In this review, we summarize the current state-of-the-art knowledge of the microglial role played in promoting the development and aggressive hallmarks of this deadly brain tumor. Particularly, we report in vitro and in vivo studies related to glioblastoma models and human patients to outline the symbiotic bidirectional interaction between microglia, lymphocytes, and tumor cells that develops during tumor progression. Furthermore, we highlight the current experimental therapeutic approaches that aim to shape these interplays, such as adeno-associated virus (AAV) delivery and CAR-T and -NK cell infusion, and to modulate the tumor microenvironment in an anti-tumoral way, thus counteracting glioblastoma growth. Full article
(This article belongs to the Special Issue Engineering the Tumor Immune Microenvironment)
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Other

18 pages, 642 KiB  
Systematic Review
Engineering the Tumor Immune Microenvironment through Minimally Invasive Interventions
by Koustav Pal and Rahul A. Sheth
Cancers 2023, 15(1), 196; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15010196 - 29 Dec 2022
Cited by 3 | Viewed by 2274
Abstract
The tumor microenvironment (TME) is a unique landscape that poses several physical, biochemical, and immune barriers to anti-cancer therapies. The rapidly evolving field of immuno-engineering provides new opportunities to dismantle the tumor immune microenvironment by efficient tumor destruction. Systemic delivery of such treatments [...] Read more.
The tumor microenvironment (TME) is a unique landscape that poses several physical, biochemical, and immune barriers to anti-cancer therapies. The rapidly evolving field of immuno-engineering provides new opportunities to dismantle the tumor immune microenvironment by efficient tumor destruction. Systemic delivery of such treatments can often have limited local effects, leading to unwanted offsite effects such as systemic toxicity and tumor resistance. Interventional radiologists use contemporary image-guided techniques to locally deliver these therapies to modulate the immunosuppressive TME, further accelerating tumor death and invoking a better anti-tumor response. These involve local therapies such as intratumoral drug delivery, nanorobots, nanoparticles, and implantable microdevices. Physical therapies such as photodynamic therapy, electroporation, hyperthermia, hypothermia, ultrasound therapy, histotripsy, and radiotherapy are also available for local tumor destruction. While the interventional radiologist can only locally manipulate the TME, there are systemic offsite recruitments of the immune response. This is known as the abscopal effect, which leads to more significant anti-tumoral downstream effects. Local delivery of modern immunoengineering methods such as locoregional CAR-T therapy combined with immune checkpoint inhibitors efficaciously modulates the immunosuppressive TME. This review highlights the various advances and technologies available now to change the TME and revolutionize oncology from a minimally invasive viewpoint. Full article
(This article belongs to the Special Issue Engineering the Tumor Immune Microenvironment)
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