As of late, reinvigoration of exhausted T cells as a form of immunotherapy against cancer has been a promising strategy. However, inconsistent results highlight the uncertainties in the current understanding of cellular exhaustion and the need for research and better treatment design. In our previous work, we utilized mathematical modeling and analysis to recapitulate and complement the biological understanding of exhaustion in response to growing tumors. The results of this work recognized that the population size of progenitor exhausted CD8+ T cells played a larger factor in tumor control compared to cytotoxic abilities. From this notion, it was theorized that exhaustion in CD4+ T cells, which are known to help coordinate and promote the size of the CD8+ T cell response, would be a significant component of tumor control. To test this theory, this paper expands on the previous mathematical framework by incorporating CD4+ T cells and the exhaustion they face in response to tumoral settings. Analysis of this model supports our theory, indicating that targeting CD4+ T cell exhaustion would have a potentially large impact on tumor burden and should be investigated along with current immunotherapy strategies of exhausted CD8+ T cell reinvigoration. Ultimately, this work narrows the scope of future research, providing a potential target for improved therapeutic efforts.

Tyler Simmons

Doron Levy

Bulletin of Mathematical Biology

BULLETIN OF MATHEMATICAL BIOLOGY 是数学生物学学会的官方期刊，传播原始研究成果和其他与生物学和数学科学接口相关的信息。贡献应该与这两个领域相关。为了适应广泛的新发展，该期刊接受各种投稿，包括：原创研究文章侧重于借助数学科学工具或新的数学工具和方法获得的新生物学见解，这些工具和方法已证明适用于生物学调查研究数学生物学教育评论评论观点，以及讨论对专业重要的问题的贡献所有贡献都经过同行评审。

The Bulletin of Mathematical Biology is the official journal of the Society for Mathematical Biology, dedicated to disseminating original research findings and information related to the interface between biology and mathematical sciences. Contributions should be relevant to both fields. The journal welcomes a variety of submissions, including original research articles that focus on new biological insights gained through mathematical tools or novel mathematical methods that have proven applicable to biological investigations; reviews on mathematical biology education; and discussions and viewpoints on issues of professional significance. All contributions undergo peer review.

《Bulletin of Mathematical Biology》是数学生物学学会的官方期刊，旨在传播原始研究成果及与生物学和数学科学交叉领域相关的信息。我们欢迎与这两个领域相关的各种投稿，包括：利用数学科学工具或新方法获得的新生物学见解的原创研究文章，这些工具和方法已被证明适用于生物学研究；数学生物学教育的评论；以及对专业重要问题的讨论和观点。所有投稿均经过同行评审。

Category	Quartile
数学	4
数学, 生物学	4
数学, 数学与计算生物学	4

Targeting CD4+ T cell Exhaustion to Improve Future Immunotherapy Strategies

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