CD4+ T Cell Help Selectively Enhances High-Avidity Tumor Antigen-Specific CD8+ T Cells

The Journal of Immunology : Official Journal of the American Association of Immunologists
Ziqiang ZhuArthur A Hurwitz

Abstract

Maintaining antitumor immunity remains a persistent impediment to cancer immunotherapy. We and others have previously reported that high-avidity CD8(+) T cells are more susceptible to tolerance induction in the tumor microenvironment. In the present study, we used a novel model where T cells derived from two independent TCR transgenic mouse lines recognize the same melanoma antigenic epitope but differ in their avidity. We tested whether providing CD4(+) T cell help would improve T cell responsiveness as a function of effector T cell avidity. Interestingly, delivery of CD4(+) T cell help during in vitro priming of CD8(+) T cells improved cytokine secretion and lytic capacity of high-avidity T cells, but not low-avidity T cells. Consistent with this observation, copriming with CD4(+) T cells improved antitumor immunity mediated by higher avidity, melanoma-specific CD8(+) T cells, but not T cells with similar specificity but lower avidity. Enhanced tumor immunity was associated with improved CD8(+) T cell expansion and reduced tolerization, and it was dependent on presentation of both CD4(+) and CD8(+) T cell epitopes by the same dendritic cell population. Our findings demonstrate that CD4(+) T cell help preferentially augments h...Continue Reading

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Citations

Mar 30, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rolf BilleskovJay A Berzofsky
Nov 14, 2018·The Journal of Clinical Investigation·Scott R WalshYonghong Wan
Feb 15, 2019·Cellular & Molecular Immunology·Pawan K GuptaMaria-Luisa Alegre
Oct 28, 2019·Nature·Elise AlspachRobert D Schreiber
Aug 2, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christopher G TuckerBrian T Fife
Mar 16, 2017·Journal of Hematology & Oncology·Le QinPeng Li
May 31, 2019·Frontiers in Immunology·Rajkumar NoubadeKristin V Tarbell
Jan 23, 2016·PloS One·Bhagwant Kaur SekhonDaniel Man-yuen Sze
Jan 1, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Denise L CecilMary L Disis
Feb 23, 2021·Frontiers in Oncology·Jianyu ChenYuhua Li
Apr 16, 2021·Frontiers in Immunology·Sarah I M SutherlandGeorgina J Clark
Dec 4, 2021·Science Immunology·Aurélien Sutra Del GalyLaurie Menger

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