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Cancers
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Chemotherapy Modulation of the Anti-Tumor Immune Response
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Chemotherapy Modulation of the Anti-Tumor Immune Response

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 July 2020) | Viewed by 17810

Special Issue Editor

Prof. Dr. William H. Gmeiner

E-Mail Website
Guest Editor
Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA
Interests: fluoropyrimidine; colorectal cancer; thymidylate synthase; DNA topoisomerase 1; DNA repair
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The efficacy of chemotherapeutic drugs is multifactorial, with direct cytotoxic effects to cancer cells being an important factor that affects outcomes, but not the sole determinant. Chemotherapy also modulates the immune antitumor response through multiple mechanistic processes that affect both the innate and the adaptive immune response.

Chemotherapy may directly alter immune cell populations, and this may affect the overall antitumor response initiated by the patient’s immune system. For example, 5-FU modulates intratumoral myeloid-derived suppressor cell (MDSC) populations, and this may contribute to increased T-cell mediated tumor cell eradication that augments the direct cytotoxic effects of 5-FU to cancer cells. Chemotherapeutic drugs may also decrease the number or activity of CD8+ cytotoxic T-lymphocytes (CTLs), natural killer (NK) cells, and other immune cell populations, which may attenuate the patient’s antitumor immune response. Further, transient depletion of immune cell populations may be followed by replenishment, making drug effects on the immune antitumor response highly schedule-dependent. Chemotherapeutic drugs also potentially affect the overall mutational burden of tumor cell populations, and this can result in increased expression of neo-antigens recognized as “non-self” and initiate an antitumor immune response toward drug-treated cells. PDL1 expression by cancer cells may also be affected by treatment with chemotherapeutic drugs, and this can modulate the efficacy of anti-PD1/anti-PDL1 checkpoint blockade therapy.

This Special Issue is directed towards summarizing novel mechanistic insights by which cytotoxic chemotherapy modulates the antitumor immune response. Reports that include clinical data supporting novel mechanistic insights in all types of cancer will be prioritized.

Prof. Dr. William H. Gmeiner
Guest Editor

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 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

  • Chemotherapy
  • Immunotherapy
  • immune response
  • T-cells
  • MDSCs
  • NK cells

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Published Papers (3 papers)

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14 pages, 3183 KiB  
Article
Cancer-Specific Immune Prognostic Signature in Solid Tumors and Its Relation to Immune Checkpoint Therapies
by Shaoli Das, Kevin Camphausen and Uma Shankavaram
Cancers 2020, 12(9), 2476; https://doi.org/10.3390/cancers12092476 - 1 Sep 2020
Cited by 38 | Viewed by 5962
Abstract
To elucidate the role of immune cell infiltration as a prognostic signature in solid tumors, we analyzed immune-function-related genes from four publicly available single-cell RNA-Seq data sets and twenty bulk tumor RNA-Seq data sets from The Cancer Genome Atlas (TCGA). Unsupervised clustering of [...] Read more.
To elucidate the role of immune cell infiltration as a prognostic signature in solid tumors, we analyzed immune-function-related genes from four publicly available single-cell RNA-Seq data sets and twenty bulk tumor RNA-Seq data sets from The Cancer Genome Atlas (TCGA). Unsupervised clustering of pan-cancer transcriptomic signature showed two major immune function types: one related to NK-, T-, and B-cell functions and the other related to monocyte, macrophage, dendritic cell, and Toll-like receptor functions. Kaplan–Meier analysis showed differential prognosis of these two groups, dependent on the cancer type. Our analysis of TCGA solid tumors with an elastic net model identified 155 genes associated with disease-free survival in different tumor types with varied influence across different cancer types. With this gene set, we computed cancer-specific prognostic immune score models for individual cancer types that predicted disease-free and overall survival. Validation of our model on available published data of immune checkpoint blockade therapies on melanoma, kidney renal cell carcinoma, non-small cell lung cancer, gastric cancer and bladder cancer confirmed that cancer-specific higher immune scores are associated with response to immunotherapy. Our analysis provides a comprehensive map of cancer-specific immune-related prognostic gene sets that are associated with immunotherapy response. Full article
(This article belongs to the Special Issue Chemotherapy Modulation of the Anti-Tumor Immune Response)
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Review

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13 pages, 633 KiB  
Review
Immunogenic Cell Death and Elimination of Immunosuppressive Cells: A Double-Edged Sword of Chemotherapy
by Jean-David Fumet, Emeric Limagne, Marion Thibaudin and Francois Ghiringhelli
Cancers 2020, 12(9), 2637; https://doi.org/10.3390/cancers12092637 - 16 Sep 2020
Cited by 43 | Viewed by 5301
Abstract
Chemotherapy is initially used to kill proliferative cells. In the current area of emerging immunotherapy, chemotherapies have shown their ability to modulate the tumor micro environment and immune response. We focus here on two main effects: first, immunogenic cell death, defined as a [...] Read more.
Chemotherapy is initially used to kill proliferative cells. In the current area of emerging immunotherapy, chemotherapies have shown their ability to modulate the tumor micro environment and immune response. We focus here on two main effects: first, immunogenic cell death, defined as a form of regulated cell death (RCD) that is sufficient to activate an adaptive immune response in immunocompetent hosts; and second, the depletion of suppressive cells, known to play a major role in immune escape and resistance to immunotherapy. In this review, we present a review of different classically used chemotherapies focusing on this double effect on immunity. These immunological effects of chemotherapy could be exploited to promote efficacy of immunotherapy. Broadening our understanding will make it possible to provide rationales for the combination of chemoimmunotherapy in early clinical trials. Full article
(This article belongs to the Special Issue Chemotherapy Modulation of the Anti-Tumor Immune Response)
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19 pages, 710 KiB  
Review
Fluoropyrimidine Modulation of the Anti-Tumor Immune Response―Prospects for Improved Colorectal Cancer Treatment
by William H. Gmeiner
Cancers 2020, 12(6), 1641; https://doi.org/10.3390/cancers12061641 - 21 Jun 2020
Cited by 29 | Viewed by 6006
Abstract
Chemotherapy modulates the anti-tumor immune response and outcomes depend on the balance of favorable and unfavorable effects of drugs on anti-tumor immunity. 5-Florouracil (5-FU) is widely used in adjuvant chemotherapy regimens to treat colorectal cancer (CRC) and provides a survival benefit. However, survival [...] Read more.
Chemotherapy modulates the anti-tumor immune response and outcomes depend on the balance of favorable and unfavorable effects of drugs on anti-tumor immunity. 5-Florouracil (5-FU) is widely used in adjuvant chemotherapy regimens to treat colorectal cancer (CRC) and provides a survival benefit. However, survival remains poor for CRC patients with advanced and metastatic disease and immune checkpoint blockade therapy benefits only a sub-set of CRC patients. Here we discuss the effects of 5-FU-based chemotherapy regimens to the anti-tumor immune response. We consider how different aspects of 5-FU’s multi-factorial mechanism differentially affect malignant and immune cell populations. We summarize recent studies with polymeric fluoropyrimidines (e.g., F10, CF10) that enhance DNA-directed effects and discuss how such approaches may be used to enhance the anti-tumor immune response and improve outcomes. Full article
(This article belongs to the Special Issue Chemotherapy Modulation of the Anti-Tumor Immune Response)
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