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7.4
5.2
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Cancers
Special Issues
New Insights in Tumor-Infiltrating Lymphocytes
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New Insights in Tumor-Infiltrating Lymphocytes

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 3347

Special Issue Editors

Dr. Serena Pellegatta

E-Mail Website
Guest Editor
Unit of Immunotherapy of Brain Tumors, Department of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria, 11, 20133 Milan, Italy
Interests: translational research in neuro-oncology, with special attention on cancer immunotherapy and immunology
Dr. Natalia Di Ianni

E-Mail Website
Guest Editor
Unit of Immunotherapy of Brain Tumors, Department of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria, 11, 20133 Milan, Italy
Interests: Immunometabolism; immunomarkers; T cell epigenetics

Special Issue Information

Dear Colleagues,

The limited success of the many promising therapeutic approaches attempted renders the treatment of many solid cancers one of the most urgent unmet needs in oncology.

Immunotherapy and cell therapy can represent an important option; however, the immune suppressive microenvironment can influence their efficacy.

We are living in an era where single-cell and multi-omics technologies are holding the potential to revolutionize the way to characterize the immune cells within the microenvironment and study their diversity, clonal distribution, pathways, and crosstalk. Tumor-infiltrating lymphocytes (TILs) are deserving of particular attention because they can be used as direct treatment mediators exerting an effective antitumor activity with low side effects per se. However, within the microenvironment, TILs engaged in tumor cell elimination become dysfunctional.

In light of this very important clinical objective, we need your innovative and original contribution to capture new insights in:

  • Prognostic significance of TILs in solid cancers;
  • Dysfunction in the relationship with the interaction with the microenvironment;
  • Potential therapeutic reprogrammability;
  • Identification of accessible markers to predict the functionality of TILs and/or their reprogramming.

We believe that this emerging area can greatly impact translational research of the immune system.

Dr. Serena Pellegatta
Dr. Natalia Di Ianni
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • tumor infiltrating lymphocytes (TILs)
  • dysfunction/exhaustion
  • reprogramming
  • tumor reactivity
  • microenvironment
  • immunometabolism
  • cell therapy

Published Papers (2 papers)

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Research

14 pages, 1604 KiB  
Article
Clinical Meaning of Stromal Tumor Infiltrating Lymphocytes (sTIL) in Early Luminal B Breast Cancer
by Esmeralda García-Torralba, Miguel Pérez Ramos, Alejandra Ivars Rubio, Esther Navarro-Manzano, Noel Blaya Boluda, Pilar de la Morena Barrio, Elisa García-Garre, Francisco Martínez Díaz, Asunción Chaves-Benito, Elena García-Martínez and Francisco Ayala de la Peña
Cancers 2023, 15(10), 2846; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15102846 - 20 May 2023
Cited by 1 | Viewed by 1357
Abstract
Luminal breast cancer (BC) is associated with less immune activation, and the significance of stromal lymphocytic infiltration (sTIL) is more uncertain than in other BC subtypes. The aim of this study was to investigate the predictive and prognostic value of sTIL in early [...] Read more.
Luminal breast cancer (BC) is associated with less immune activation, and the significance of stromal lymphocytic infiltration (sTIL) is more uncertain than in other BC subtypes. The aim of this study was to investigate the predictive and prognostic value of sTIL in early luminal BC. The study was performed with an observational design in a prospective cohort of 345 patients with predominantly high-risk luminal (hormone receptor positive, HER2 negative) BC and with luminal B features (n = 286), in which the presence of sTIL was analyzed with validated methods. Median sTIL infiltration was 5% (Q1–Q3 range (IQR), 0–10). We found that sTIL were associated with characteristics of higher biological and clinical aggressiveness (tumor and lymph node proliferation and stage, among others) and that the percentage of sTIL was predictive of pathologic complete response in patients treated with neoadjuvant chemotherapy (OR: 1.05, 95%CI 1.02–1.09, p < 0.001). The inclusion of sTIL (any level of lymphocytic infiltration: sTIL > 0%) in Cox regression multivariable prognostic models was associated with a shorter relapse-free interval (HR: 4.85, 95%CI 1.33–17.65, p = 0.016) and significantly improved its performance. The prognostic impact of sTIL was independent of other clinical and pathological variables and was mainly driven by its relevance in luminal B BC. Full article
(This article belongs to the Special Issue New Insights in Tumor-Infiltrating Lymphocytes)
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15 pages, 1930 KiB  
Article
Tumor Microenvironment and Immune Response in Lip Cancer
by Anastasia G. Gkegka, Michael I. Koukourakis, Maria Lambropoulou and Alexandra Giatromanolaki
Cancers 2023, 15(5), 1478; https://doi.org/10.3390/cancers15051478 - 25 Feb 2023
Cited by 1 | Viewed by 1429
Abstract
Tumor-infiltrating lymphocytes (TILs) play a significant role in cancer progression and prognosis of patients. The tumor microenvironment (TME) may affect the anti-tumor immune response. We examined the TIL and tertiary lymphoid structure (TLS) density in the invading front and inner tumor stroma, and [...] Read more.
Tumor-infiltrating lymphocytes (TILs) play a significant role in cancer progression and prognosis of patients. The tumor microenvironment (TME) may affect the anti-tumor immune response. We examined the TIL and tertiary lymphoid structure (TLS) density in the invading front and inner tumor stroma, and the lymphocyte subpopulation (CD8, CD4, FOXP3) density in 60 squamous cell carcinomas of the lip. Analysis was performed in parallel with markers of hypoxia (hypoxia-inducible factor (HIF1α), lactate dehydrogenase (LDHA)) and angiogenesis. Low TIL density in the invading tumor front was related with larger tumor size (p = 0.05), deep invasion (p = 0.01), high smooth-muscle actin (SMA) expression (p = 0.01), and high HIF1α and LDH5 expression (p = 0.04). FOXP3+ TILs infiltration and FOXP3+/CD8+ ratios were higher in inner tumor areas, linked with LDH5 expression, and higher MIB1 proliferation index (p = 0.03) and SMA expression (p = 0.001). Dense CD4+ lymphocytic infiltration in the invading front is related to high tumor-budding (TB) (p = 0.04) and angiogenesis (p = 0.04 and p = 0.006, respectively). Low CD8+ TIL density, high CD20+ B-cell density, high FOXP3+/CD8+ ratio and high CD68+ macrophage presence characterized tumors with local invasion (p = 0.02, 0.01, 0.02 and 0.006, respectively). High angiogenic activity was linked with high CD4+, FOXP3+, and low CD8+ TIL density (p = 0.05, 0.01 and 0.01, respectively), as well as high CD68+ macrophage presence (p = 0.003). LDH5 expression was linked with high CD4+ and FOXP3+ TIL density (p = 0.05 and 0.01, respectively). Further research is needed to explore the prognostic and therapeutic value of TME/TIL interactions. Full article
(This article belongs to the Special Issue New Insights in Tumor-Infiltrating Lymphocytes)
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