Abstract 1172: Association between CD8+ PD-1+ T cell infiltration levels and improved response to total neoadjuvant therapy in mismatch-repair proficient locally advanced rectal cancer

Abstract Background: The tumor microenvironment plays a major role in colorectal cancer progression, dissemination, and response to therapy. As a mechanism of tumor immunity, CD8+ tumor infiltrating lymphocytes have been shown to express PD-1 in response to clonal neoantigens of tumors. We hypothesized that high levels of CD8+ PD-1+ T cell infiltration prior to treatment initiation may correlate with improved response to total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC). Methods: We analyzed untreated endoscopic biopsies from 159 patients diagnosed with stage II (n=25) or III (n=134), mismatch-repair proficient rectal adenocarcinoma. All patients were treated with TNT, consisting of either induction chemotherapy followed by chemoradiation (n=108) or chemoradiation followed by consolidative chemotherapy (n=51). FFPE blocks from each biopsy were sectioned into slides for H p=0. 006, log-rank test). Patients in the highest tertile of intratumoral PD-1 expression also had improved response (56% vs. 25%, p=0. 002) and DFS (88% vs. 67%, p=0. 034). CD8 and PD-1 levels were strongly correlated with each other (R=0. 72, p0. 001, Spearman correlation). Finally, the 41 patients who met criteria for top tertiles of CD8 and PD-1 expression had higher CR rates (66% vs. 32%, p0. 001) and better 5-year DFS (97% vs. 70%, p=0. 002) than the other patients. Conclusions: Higher levels of CD8+ and PD-1+ tumor infiltrating lymphocytes on pre-treatment biopsies are associated with improved response to TNT and disease free survival in LARC patients. Citation Format: Christina Lee, Chin-Tung Chen, Nil Urganci, Fan Wu, Canan Firat, Hannah Williams, Evan Seffar, Parisa Malekzadeh, Walid K. Chatila, Jinru Shia, Julio Garcia-Aguilar, Francisco Sanchez-Vega. Association between CD8+ PD-1+ T cell infiltration levels and improved response to total neoadjuvant therapy in mismatch-repair proficient locally advanced rectal cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 1172.