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Response, Toxicity and Resistance to Immune Checkpoint Inhibitor Cancer Therapy: Biological Mechanisms and Promising Solutions to Improve Future Outcomes

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

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 14032

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Special Issue Editors

Dr. Julien Péron

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Guest Editor

Cancer Institute of the Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, 69310 Pierre-Bénite, France
Interests: breast cancer; immunotherapy; clinical trials; multicriteria analyses

Dr. Amélie Boespflug

E-Mail Website
Guest Editor

Dermatology department, Centre Hospitalier Lyon Sud, 69310 Pierre-Bénite, France
Interests: melanoma; immunotherapy; MAPkinase pathway

Special Issue Information

Immune checkpoint inhibitors, including PD-1/PD-L1 and CTLA4 blockade therapy, have revolutionized the treatment landscape of several malignancies. However, only a minority of patients experience a positive response to immune checkpoint inhibitors, and outcomes have been disappointing in several tumor types.

Many research works have been conducted to understand the mechanisms underlying these heterogeneous outcomes, and many promising leads are currently being investigated. Developing our understanding of the complexity of anticancer immune response will support the development of the next generation of immune therapies. This complexity should certainly include the role of the inflammasome, epithelial–mesenchymal transition, microbiome interaction with the immune system, tumor-activated molecular pathways such as the MAPkinase pathway, T-cell dysfunction, and of microRNAs. The role of abscopal effect in the priming of the immune response, and the role of other systemic therapies designed to enhance the immune response at later stages, can provide empirical knowledge on future treatment strategies.

This Special Issue will highlight the current state of the art in predictive biomarkers of tumor immune response and/or toxicity and future prospects for combined therapies.

Dr. Julien Péron
Dr. Amélie Boespflug
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

immunotherapy
immune checkpoint inhibitors
predictive biomarkers
resistance
toxicity

Published Papers (4 papers)

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Research

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14 pages, 823 KiB

Open AccessArticle

Serum sCD25 Protein as a Predictor of Lack of Long-Term Benefits from Immunotherapy in Non-Small Cell Lung Cancer: A Pilot Study

by Anna Siemiątkowska, Maciej Bryl, Katarzyna Kosicka-Noworzyń, Jakub Tvrdoň, Iwona Gołda-Gocka, Aleksander Barinow-Wojewódzki and Franciszek K. Główka

Cancers 2021, 13(15), 3702; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13153702 - 23 Jul 2021

Cited by 5 | Viewed by 2711

Abstract

Prognosis of advanced non-small cell lung carcinoma (NSCLC) is poor. Even though it can improve with anti-PD-1/PD-L1 agents, most patients do not respond to treatment. We hypothesized that the serum soluble form of the unit α of the interleukin-2 receptor (sCD25) could be used as a biomarker of successful immunotherapy in NSCLC. We recruited patients dosed with atezolizumab (n = 42) or pembrolizumab (n = 20) and collected samples at baseline and during the treatment. Levels of sCD25 were quantified with the ELISA kits. Patients with a high sCD25 at baseline (sCD25.0 ≥ 5.99 ng/mL) or/and at the end of the fourth treatment cycle (sCD25.4 ≥ 7.73 ng/mL) progressed faster and lived shorter without the disease progression and serious toxicity. None of the patients with high sCD25 at both time points continued therapy longer than 9.3 months, while almost 40% of patients with low sCD25 were treated for ≥12.3 months. There was a 6.3-times higher incidence of treatment failure (HR = 6.33, 95% CI: 2.10–19.06, p = 0.001) and a 6.5-times higher incidence of progression (HR = 6.50, 95% CI: 2.04–20.73, p = 0.002) in patients with high compared with low sCD25.0 and sCD25.4. Serum levels of sCD25 may serve as a non-invasive biomarker of long-term benefits from the anti-PD-1/PD-L1s in NSCLC. Full article

(This article belongs to the Special Issue Response, Toxicity and Resistance to Immune Checkpoint Inhibitor Cancer Therapy: Biological Mechanisms and Promising Solutions to Improve Future Outcomes)

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15 pages, 691 KiB

Open AccessArticle

Investigating the Impact of Immune-Related Adverse Events, Glucocorticoid Use and Immunotherapy Interruption on Long-Term Survival Outcomes

by Charline Lafayolle de la Bruyère, Pierre-Jean Souquet, Stéphane Dalle, Pauline Corbaux, Amélie Boespflug, Michaël Duruisseaux, Lize Kiakouama-Maleka, Thibaut Reverdy, Madeleine Maugeais, Gulsum Sahin, Denis Maillet and Julien Péron

Cancers 2021, 13(10), 2365; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13102365 - 14 May 2021

Cited by 8 | Viewed by 1778

Abstract

It remains unclear whether immune-related adverse events (irAEs) and glucocorticoid use could impact long-term outcomes in patients treated for solid tumors with immune checkpoint inhibitors (ICI). All patients treated with a single-agent ICI for any advanced cancer were included in this retrospective unicentric study. The objectives were to assess the impact of grade ≥3 irAEs, glucocorticoid use and the interruption of immunotherapy on progression-free survival (PFS) and overall survival (OS). In this 828-patient cohort, the first occurrence of grade ≥3 irAEs had no significant impact on PFS or OS. Glucocorticoid administration for the irAEs was associated with a significantly shorter PFS (adjusted HR 3.0; p = 0.00040) and a trend toward shorter OS. ICI interruption was associated with a significantly shorter PFS (adjusted HR 3.5; p < 0.00043) and shorter OS (HR 4.5; p = 0.0027). Glucocorticoid administration and ICI interruption were correlated. In our population of patients treated with single agent ICI, grade ≥3 irAEs did not impact long-term outcomes. However, the need for glucocorticoids and the interruption of immunotherapy resulted in poorer long-term outcomes. The impact of grade ≥3 irAEs reported in other studies might then be explained by the management of the irAEs. Full article

(This article belongs to the Special Issue Response, Toxicity and Resistance to Immune Checkpoint Inhibitor Cancer Therapy: Biological Mechanisms and Promising Solutions to Improve Future Outcomes)

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Review

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30 pages, 1812 KiB

Open AccessEditor’s ChoiceReview

Biomarkers of Response and Resistance to Immunotherapy in Microsatellite Stable Colorectal Cancer: Toward a New Personalized Medicine

by Nicolas Huyghe, Elena Benidovskaya, Philippe Stevens and Marc Van den Eynde

Cancers 2022, 14(9), 2241; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14092241 - 29 Apr 2022

Cited by 25 | Viewed by 4280

Abstract

Immune Checkpoint Inhibitors (ICIs) are well recognized as a major immune treatment modality for multiple types of solid cancers. However, for colorectal cancer (CRC), ICIs are only approved for the treatment of Mismatch-Repair-Deficient and Microsatellite Instability-High (dMMR/MSI-H) tumors. For the vast majority of CRC, that are not dMMR/MSI-H, ICIs alone provide limited to no clinical benefit. This discrepancy of response between CRC and other solid cancers suggests that CRC may be inherently resistant to ICIs alone. In translational research, efforts are underway to thoroughly characterize the immune microenvironment of CRC to better understand the mechanisms behind this resistance and to find new biomarkers of response. In the clinic, trials are being set up to study biomarkers along with treatments targeting newly discovered immune checkpoint molecules or treatments combining ICIs with other existing therapies to improve response in MSS CRC. In this review, we will focus on the characteristics of response and resistance to ICIs in CRC, and discuss promising biomarkers studied in recent clinical trials combining ICIs with other therapies. Full article

(This article belongs to the Special Issue Response, Toxicity and Resistance to Immune Checkpoint Inhibitor Cancer Therapy: Biological Mechanisms and Promising Solutions to Improve Future Outcomes)

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22 pages, 1333 KiB

Open AccessEditor’s ChoiceReview

Advances in Immunotherapy for the Treatment of Adult Glioblastoma: Overcoming Chemical and Physical Barriers

by Mirna Lechpammer, Rohan Rao, Sanjit Shah, Mona Mirheydari, Debanjan Bhattacharya, Abigail Koehler, Donatien Kamdem Toukam, Kevin J. Haworth, Daniel Pomeranz Krummel and Soma Sengupta

Cancers 2022, 14(7), 1627; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14071627 - 23 Mar 2022

Cited by 8 | Viewed by 4351

Abstract

Glioblastoma, or glioblastoma multiforme (GBM, WHO Grade IV), is a highly aggressive adult glioma. Despite extensive efforts to improve treatment, the current standard-of-care (SOC) regimen, which consists of maximal resection, radiotherapy, and temozolomide (TMZ), achieves only a 12–15 month survival. The clinical improvements achieved through immunotherapy in several extracranial solid tumors, including non-small-cell lung cancer, melanoma, and non-Hodgkin lymphoma, inspired investigations to pursue various immunotherapeutic interventions in adult glioblastoma patients. Despite some encouraging reports from preclinical and early-stage clinical trials, none of the tested agents have been convincing in Phase III clinical trials. One, but not the only, factor that is accountable for the slow progress is the blood–brain barrier, which prevents most antitumor drugs from reaching the target in appreciable amounts. Herein, we review the current state of immunotherapy in glioblastoma and discuss the significant challenges that prevent advancement. We also provide thoughts on steps that may be taken to remediate these challenges, including the application of ultrasound technologies. Full article

(This article belongs to the Special Issue Response, Toxicity and Resistance to Immune Checkpoint Inhibitor Cancer Therapy: Biological Mechanisms and Promising Solutions to Improve Future Outcomes)

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