Abstract 6550: Cancer-associated fibroblast-targeted near-infrared photoimmunotherapy induces tumor specific memory T cells from TDLNs

Abstract Introduction: Our laboratory previously showed that cancer-associated fibroblasts (CAFs) suppress antitumor immunity in the tumor microenvironment (TME) and that CAF-targeted near-infrared photoimmunotherapy (CAF-PIT) improves antitumor immunity in the TME and reduces tumor size by TME remodeling. Dendritic cells have been suggested to migrate from the TME to the tumor drainage lymph nodes (TDLNs) and promote the proliferation of tumor-specific memory T cells and their migration to the tumor. We hypothesized that CAFs inhibit this process. Methods: To evaluate the effect of memory T cells in the TME on prognosis, we evaluated memory T cells in the TME of clinical specimens of esophageal squamous cell carcinoma using immunohistochemistry with a CD45RO antibody. We also examined its correlation with area of CAF evaluated by α-SMA antibody in previous studies. We evaluated tumor-specific memory T cells and dendritic cells in the TME and ipsilateral inguinal lymph nodes (TDLNs) and contralateral inguinal lymph nodes(non-TDLNs) in flank subcutaneous tumor models of MC38, a mouse colon cancer tumor strain that is highly immunogenic and can be used to evaluate tumor-specific T cells using H-2Kb p15E tetramers. We created CAF-rich models co-inoculated with MEF and evaluated the effect of CAFs, CAF-PIT, and TDLNs using flow cytometry. Results: Among patients with esophageal squamous cell carcinoma, those with a high number of CD45RO-positive cells in the TME had a better prognosis. Furthermore, in cases with T2 or deeper, there was a negative correlation with area of CAF which suggested that CAF might inhibit the migration of memory T cells.Evaluation of tumor-specific T cells in a mouse model showed that TDLNs contain more tumor-specific T cells and dendritic cells than non-TDLNs. In addition, tumor-specific T cells were present mainly as effector and central memory T cells in the TME and TDLNs, respectively.In CAF-rich tumor mouse, tumor-specific effector memory T cells in the TME were significantly lower than in CAF-poor tumor mouse, and tumor-specific central memory T cells in the TDLNs were lower. When CAFs were removed by CAF-PIT, the number of tumor-specific effector memory T cells in the TME increased significantly. In addition, resecting TDLNs before FAP-PIT decreased the number of tumor-specific effector memory T cells in the TME and weakened the therapeutic effect. Conclusion: CAF-PIT induces tumor-specific memory T cells from TDLNs via TME remodeling. Citation Format: Akito Shimizu, Kazuhiro Noma, Tatsuya Takahashi, Tasuku Matsumoto, Seitaro Nishimura, Yasushige Takeda, Hijiri Matsumoto, Tomoyoshi Kunitomo, Masashi Hashimoto, Hajime Kashima, Maeda Naoaki, Satoru Kikuchi, Shunsuke Tanabe, Toshiaki Ohara, Hiroshi Tazawa, Hisataka Kobayashi, Toshiyoshi Fujiwara. Cancer-associated fibroblast-targeted near-infrared photoimmunotherapy induces tumor specific memory T cells from TDLNs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6550.