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Harnessing the IL-21-BATF Pathway in the $CD8^{+}$ T Cell Anti-Tumor Response
| Content Provider | MDPI |
|---|---|
| Author | Topchyan, Paytsar Xin, Gang Chen, Yao Zheng, Shikan Burns, Robert Shen, Jian Kasmani, Moujtaba Kudek, Matthew Yang, Na Cui, Weiguo |
| Copyright Year | 2021 |
| Description | In cancer, CD8+ T cells enter a dysfunctional state which prevents them from effectively targeting and killing tumor cells. Tumor-infiltrating CD8+ T cells consist of a heterogeneous population of memory-like progenitor, effector, and terminally exhausted cells that exhibit differing functional and self-renewal capacities. Our recently published work has shown that interleukin (IL)-21-producing CD4+ T cells help to generate effector CD8+ T cells within the tumor, which results in enhanced tumor control. However, the molecular mechanisms by which CD4+ helper T cells regulate the differentiation of effector CD8+ T cells are not well understood. In this study, we found that Basic Leucine Zipper ATF-Like Transcription Factor (BATF), a transcription factor downstream of IL-21 signaling, is critical to maintain CD8+ T cell effector function within the tumor. Using mixed bone marrow chimeras, we demonstrated that CD8+ T cell-specific deletion of BATF resulted in impaired tumor control. In contrast, overexpressing BATF in CD8+ T cells enhanced effector function and resulted in improved tumor control, bypassing the need for CD4+ helper T cells. Transcriptomic analyses revealed that BATF-overexpressing CD8+ T cells had increased expression of costimulatory receptors, effector molecules, and transcriptional regulators, which may contribute to their enhanced activation and effector function. Taken together, our study unravels a previously unappreciated CD4+ T cell-derived IL-21–BATF axis that could provide therapeutic insights to enhance effector CD8+ T cell function to fight cancer. |
| Starting Page | 1263 |
| e-ISSN | 20726694 |
| DOI | 10.3390/cancers13061263 |
| Journal | Cancers |
| Issue Number | 6 |
| Volume Number | 13 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-03-12 |
| Access Restriction | Open |
| Subject Keyword | Cancers Immunology Batf Il-21 Cd8 T Cells Cd4 T Cells Adoptive Cell Therapy Cancer Immunotherapy |
| Content Type | Text |
| Resource Type | Article |
