American Association for Cancer Research
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Figure S4 from IL3-Driven T Cell–Basophil Crosstalk Enhances Antitumor Immunity

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posted on 2024-07-02, 07:22 authored by Jian Wei, Colleen L. Mayberry, Xiaoting Lv, Fangyan Hu, Taushif Khan, Natalie A. Logan, John J. Wilson, John D. Sears, Damien Chaussabel, Chih-Hao Chang

Co-culture with bulk splenocytes potentiates antitumor activity of CD8+ T cells

Funding

National Cancer Institute (NCI)

United States Department of Health and Human Services

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Jackson Laboratory (JAX)

American Cancer Society (ACS)

V Foundation for Cancer Research (VFCR)

American Association of Immunologists (AAI)

National Natural Science Foundation of China (NSFC)

Natural Science Foundation of Shandong Province (山东省自然科学基金)

Taishan Scholar Project of Shandong Province

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ARTICLE ABSTRACT

Cytotoxic T lymphocytes (CTL) are pivotal in combating cancer, yet their efficacy is often hindered by the immunosuppressive tumor microenvironment, resulting in CTL exhaustion. This study investigates the role of interleukin-3 (IL3) in orchestrating antitumor immunity through CTL modulation. We found that intratumoral CTLs exhibited a progressive decline in IL3 production, which was correlated with impaired cytotoxic function. Augmenting IL3 supplementation, through intraperitoneal administration of recombinant IL3, IL3-expressing tumor cells, or IL3-engineered CD8+ T cells, conferred protection against tumor progression, concomitant with increased CTL activity. CTLs were critical for this therapeutic efficacy as IL3 demonstrated no impact on tumor growth in Rag1 knockout mice or following CD8+ T-cell depletion. Rather than acting directly, CTL-derived IL3 exerted its influence on basophils, concomitantly amplifying antitumor immunity within CTLs. Introducing IL3-activated basophils retarded tumor progression, whereas basophil depletion diminished the effectiveness of IL3 supplementation. Furthermore, IL3 prompted basophils to produce IL4, which subsequently elevated CTL IFNγ production and viability. Further, the importance of basophil-derived IL4 was evident from the absence of benefits of IL3 supplementation in IL4 knockout tumor-bearing mice. Overall, this research has unveiled a role for IL3-mediated CTL–basophil cross-talk in regulating antitumor immunity and suggests harnessing IL3 sustenance as a promising approach for optimizing and enhancing cancer immunotherapy.See related Spotlight, p. 798

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