Adoptively transferred Th17 cells cooperate with host B cells to achieve durable tumor immunity
CD4<sup>+</sup> T helper cells play an important role in adoptive T cell therapy (ACT) success, but it remains unclear which subset is most therapeutic and how they eliminate tumors. We find that tumor-specific Th17 cells eradicate melanoma more effectively than other CD4<sup>+</sup> subsets and protect against distant metastases by unique orchestration of host immunity. Donor Th17 cells require host B cells -but not T cells- for tumor regression. Th17 cells induce B cell proliferation, activation, and differentiation, while B cells augment Th17 cell polyfunctionality by enhancing IL-21 production. Th17 and B cells colocalize in lymphoid tissues, where Th17 cells induce germinal centers and tumor-reactive antibodies via IL-21 production and CD40L costimulation. Furthermore, these tumor-specific antibodies provide partial protection against tumor challenge. Herein, we reveal that adoptively transferred Th17 cells cooperate with B cells to drive sustained immunity, demonstrating a role for endogenous B cell responses in effective CD4<sup>+</sup> ACT.
Authors
- Bhavana Pavuluri
- Pawel Muranski (ORCID: https://orcid.org/0000-0002-4446-6385)
- Guillermo O. Rangel Rivera (ORCID: https://orcid.org/0000-0001-9364-6385)
- Ayana T. Ruffin (ORCID: https://orcid.org/0000-0002-5837-5871)
- Megen C Wittling (ORCID: https://orcid.org/0000-0002-3631-4955)
- Gregory B. Lesinski (ORCID: https://orcid.org/0000-0002-8787-7678)
- Soundharya Kumaresan (ORCID: https://orcid.org/0000-0001-5946-1678)
- Natalie K. Horvat (ORCID: https://orcid.org/0000-0003-2789-8132)
- Chrystal Mary Paulos (ORCID: https://orcid.org/0000-0002-0784-2601)
- Megan M. Wyatt (ORCID: https://orcid.org/0000-0003-1316-260X)
- Anna C. Cole (ORCID: https://orcid.org/0000-0002-2832-2824)
- Aubrey S. Smith (ORCID: https://orcid.org/0000-0003-3693-4262)
- Jeremy M. Boss (ORCID: https://orcid.org/0000-0002-2432-1840)
- Amalia M. Rivera Reyes (ORCID: https://orcid.org/0000-0003-3675-2936)
- Hannah M. Knochelmann (ORCID: https://orcid.org/0000-0003-0644-123X)
Institutions
- Emory University (US)
- Columbia University Irving Medical Center (US)
Publication Details
- Journal
- Cancer Cell
- Published
- 2025-07-24
- DOI
- https://doi.org/10.1016/j.ccell.2025.07.001
- Citations
- 7
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 7.32