Intratumoral and peritumoral lymphocytic responses correlate with survival in rectal cancer

Background: Colorectal cancer (CRC) with high level of microsatellite instability (MSI-H) is associated with improved survival. Histopathological assessment of prominent infiltration of lymphocytes in tumor microenvironment (TME), including intratumoral lymphocytic response (ILR) and peritumoral lymphocytic response (PLR), was utilized to predict MSI-H. However, the direct pathological evidence of lymphocytic response predicting survival of rectal cancer is lacking due to the predominant neoadjuvant concurrent chemoradiotherapy (CCRT) treatment. This study aims to identify whether the phenotype of PLR and ILR is associated with the clinical outcome of locally-advanced rectal cancer receiving definitive surgery followed by adjuvant CCRT. Methods: From 2005 to 2018, among the 121 patients enrolled from MacKay Memorial Hospital, 55 specimen was assessable for lymphocytic response. ILR and PLR were assessed according to the cancer reporting protocol released by the College of American Pathologists (CAP). Based on positive or negative ILR/PLR, we categorized each patient as one of the four groups: ILR+/PLR+, ILR+/PLR−, ILR−/PLR+, or ILR−/PLR−. Results: ILR−/PLR− was significantly associated with poorer overall survival, compared to either positive lymphocytic response of ILR or PLR. Multivariate analysis revealed ILR−/PLR− as a significant risk factor for overall survival after adjusting with clinical characteristics. Conclusions: Lymphocytic response in tumor microenvironment (TME) can be a predictor for poor survival outcome and a potential indicator for immunotherapy.