# Reprogramming tumor-reactive CD8 T cells by targeting the IL-21-BATF pathway to treat melanoma > **NIH NIH F30** · VERSITI BLOOD HEALTH, INC. · 2020 · $47,610 ## Abstract Project Summary Advanced melanoma is a major target of cancer immunotherapy research due to its poor survival rate even with recent treatment advances. Current strategies focus on CD8 T cells which enter a dysfunctional state in the tumor microenvironment. Recent studies have found that intratumoral 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. However, the cellular and molecular processes involved in the differentiation of these subsets within melanoma is not well understood. Exploring the intricacies of CD8 T cell differentiation towards an effector profile can identify novel immunotherapeutic targets. Thus, the long-term goal of this project is to elucidate the mechanisms regulating effector CD8 T cell differentiation and function in melanoma. CD4 T cell production of cytokines provide help to CD8 T cells. Recent studies have uncovered the cytokine IL- 21 as a critical signal produced by CD4 T cells to help promote CD8 T cell maintenance in chronic infection. However, the direct effects of IL-21 produced by CD4 T cells on CD8 T cell differentiation and function in cancer remains unknown. Preliminary data presented in this proposal suggest that IL-21 producing CD4 T cells induce an effective antitumor response dependent on CD8 T cells. Additionally, it has been previously found that IL-21 signaling induces the transcription factor BATF, which is known to cooperatively bind with IRF4 to induce changes in the chromatin landscape. This has led to the hypothesis that the IL-21-BATF pathway enhances melanoma-infiltrating effector CX3CR1+ CD8 T cells and their function via BATF-IRF4 mediated transcriptional regulation. Aim 1 will determine if adoptively transferred IL-21-producing CD4 T cells enhance effector CX3CR1+ CD8 T cell differentiation. The effect of CD4 T cell-derived IL-21 on CD8 T cell differentiation and function will be determined in vivo. Then, it will be determined if IL-21R signaling is intrinsically necessary for the CD8 T cell response to IL-21 producing CD4 T cell help. Aim 2 will investigate the mechanism of BATF-mediated tumor-infiltrating CD8 T cell differentiation. These experiments will determine if BATF-IRF4 interaction is necessary to promote tumor-infiltrating CX3CR1+ CD8 T cells. Furthermore, changes in BATF-mediated chromatin accessibility in CD8 T cell differentiation and function will be assessed. This proposal will help in understanding how CD8 T cells differentiate and function in melanoma. This is in line with the mission of NCI, as the results of this project could lead to the identification of BATF as a novel therapeutic mechanism to enhance effector CD8 T cell differentiation to fight cancer. ## Key facts - **NIH application ID:** 9906544 - **Project number:** 1F30CA246920-01 - **Recipient organization:** VERSITI BLOOD HEALTH, INC. - **Principal Investigator:** Paytsar Topchyan - **Activity code:** F30 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $47,610 - **Award type:** 1 - **Project period:** 2020-01-01 → 2023-12-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/9906544 ## Citation > US National Institutes of Health, RePORTER application 9906544, Reprogramming tumor-reactive CD8 T cells by targeting the IL-21-BATF pathway to treat melanoma (1F30CA246920-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9906544. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*