Modulating CD4+ T Cells for Cancer Immunotherapy: Emerging Strategies and Applications

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Cancer Vaccines and Immunotherapy".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 1492

Special Issue Editor


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Guest Editor
School of Medicine, University of Missouri, Columbia, MO, USA
Interests: immunomodulation; autoimmunity; transplantation; cancer immunoprevention; immunotherapy

Special Issue Information

Dear Colleagues,

Immunomodulation is one of the key strategies used to fight cancer. It is the process of modifying the immune system to enhance its ability to recognize and eradicate cancer. As CD4+ T cells are key in regulating various effector immune responses, modulating the function of these cells to generate a robust effector response while overcoming the immunosuppressive tumor microenvironment is paramount for effective cancer immunotherapy. The differentiation of CD4+ T cells into various subsets with specialized functions is driven by various factors, including antigen stimulation, cytokines, and environmental cues. CD4+ T cells may promote antitumor immunity via different mechanisms, such as enhancing antigen presentation; the costimulation, activation, and homing of effector immune cells to the tumor site; and the direct killing of cancer cells. Several cancer vaccine approaches targeting CD4+ T cells for the acquisition of effector responses have shown promise in the clinic. Harnessing the full potential of the immune system to fight cancer still requires a deeper understanding of CD4+ T cell activation, acquisition of the effector function, and sustaining a durable and robust antitumor immune response.

In this Special Issue, we invite scholars to submit their work focusing on the role of CD4+ T cells in cancer immunotherapy and the design of immunomodulatory strategies, including vaccines, to regulate these cells for robust therapeutic immune response against cancer.

Prof. Dr. Haval Shirwan
Guest Editor

Manuscript Submission Information

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Keywords

  • CD4+ T cells
  • immunomodulation
  • cancer immunotherapy
  • cancer vaccines
  • immunotherapeutic agents

Published Papers (1 paper)

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Research

17 pages, 4578 KiB  
Article
Oncolytic Adenovirus Armed with a Novel Agonist of the CD137 Immune Checkpoint Stimulator Suppresses Tumor Growth
by Martin R. Ramos-Gonzalez, Mohammad Tarique, Lalit Batra, Feyza Arguc, Rodolfo Garza-Morales, Haval Shirwan, Esma S. Yolcu and Jorge G. Gomez-Gutierrez
Vaccines 2024, 12(3), 340; https://doi.org/10.3390/vaccines12030340 - 21 Mar 2024
Viewed by 1271
Abstract
Natural 4-1BBL (CD137L) is a cell membrane-bound protein critical to the expansion, effector function, and survival of CD8+ T cells. We reported the generation of an active soluble oligomeric construct, SA-4-1BBL, with demonstrated immunoprevention and immunotherapeutic efficacy in various mouse tumor models. [...] Read more.
Natural 4-1BBL (CD137L) is a cell membrane-bound protein critical to the expansion, effector function, and survival of CD8+ T cells. We reported the generation of an active soluble oligomeric construct, SA-4-1BBL, with demonstrated immunoprevention and immunotherapeutic efficacy in various mouse tumor models. Herein, we developed an oncolytic adenovirus (OAd) for the delivery and expression of SA-4-1BBL (OAdSA-4-1BBL) into solid tumors for immunotherapy. SA-4-1BBL protein expressed by this construct produced T-cell proliferation in vitro. OAdSA-4-1BBL decreased cell viability in two mouse lung cancer cell lines, TC-1 and CMT64, but not in the non-cancerous lung MM14.Lu cell line. OAdSA-4-1BBL induced programmed cell death types I and II (apoptosis and autophagy, respectively), and autophagy-mediated adenosine triphosphate (ATP) release was also detected. Intratumoral injection of OAdSA-4-1BBL efficiently expressed the SA-4-1BBL protein in the tumors, resulting in significant tumor suppression in a syngeneic subcutaneous TC-1 mouse lung cancer model. Tumor suppression was associated with a higher frequency of dendritic cells and an increased infiltration of cytotoxic CD8+ T and NK cells into the tumors. Our data suggest that OAdSA-4-1BBL may present an efficacious alternative therapeutic strategy against lung cancer as a standalone construct or in combination with other immunotherapeutic modalities, such as immune checkpoint inhibitors. Full article
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