Prognostic Relevance of Immunosuppressive CD155/TIGIT Signaling in Locally Advanced Rectal Cancer Patients With Neoadjuvant Chemoradiotherapy

Background/Aim: The CD155/TIGIT axis has recently emerged as a promising immunotherapeutic target in several malignancies. However, its prognostic relevance within the tumor microenvironment (TME) in patients with locally advanced rectal cancer (LARC) who have received neo-adjuvant chemoradiotherapy (neoCRT) remains unclarified. Materials and Methods: The levels of tumor CD155 and TIGIT⁺ T cells in pair-matched pre-neoCRT biopsies and post-neoCRT surgical tissues were evaluated in 110 LARC tissues using immunohistochemistry. The relationship between CD155, TIGIT⁺ T cells, and other clinicopathological parameters was analyzed. Results: The level of tumor CD155 was significantly increased in the post-neoCRT surgical tissues, compared to pre-neoCRT biopsies (p=0.0491). Moreover, tumor CD155 expression correlated with increased risk of local recurrence (p=0.016) and the infiltration of CD3⁺ T cells in the post-neoCRT surgical tissues (p=0.026). Patients with high tumor CD155 were significantly associated with worsen 10-year disease-free survival (DFS), suggesting the prognostic value of tumor CD155 on DFS in LARC patients who received neoCRT treatment. However, no significant association was observed between TIGIT⁺ T cells and DFS in these patients. Conclusion: Tumor CD155 may play a pivotal role in the response to neoCRT treatment through alternative immunological mechanisms and could become a novel immunotherapeutic target for LARC patients.