RT Journal Article SR Electronic T1 Stromal CD4 (+) T Cell Subsets Mediate Antitumor Cytotoxic Immune Responses in Human Colorectal Carcinoma JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 3899 OP 3906 DO 10.21873/anticanres.17217 VO 44 IS 9 A1 FUKUSHIMA, GENTARO A1 SATO, EIICHI A1 UDO, RYUTARO A1 TAGO, TOMOYA A1 KASAHARA, KENTA A1 MAZAKI, JUNICHI A1 IWASAKI, KENICHI A1 ENOMOTO, MASANOBU A1 ISHIZAKI, TETSUO A1 NAGAKAWA, YUICHI YR 2024 UL http://ar.iiarjournals.org/content/44/9/3899.abstract AB Background/Aim: The local immune response in colorectal cancer is closely related to prognosis and therapeutic efficacy. In this study, histological analyses were performed to determine the phenotype of tumor-infiltrating lymphocytes (TILs) and their infiltration in the stromal and intratumoral regions, aiming to elucidate their interactions and prognostic effects. Patients and Methods: Multiplex fluorescent labeling was performed using surgically resected colorectal cancer specimens to investigate the infiltration of CD45RO (+) TILs, which exhibit cytotoxicity, and subsets of CD4 (+) TILs, identified by their characteristic transcription factor expression. Results: The degree of CD45RO (+) TIL infiltration in the entire observation field or stromal area was not associated with prognosis. However, a high degree of infiltration in the tumor nest (intratumoral area) was significantly associated with a favorable prognosis. CD4 (+) TILs and their subsets were not associated with prognosis. However, stratified analyses revealed that a high degree of infiltration of stromal CD4 (+) TILs and the subsets T helper (Th)1, Th2, Th17, and regulatory T cells is necessary for the association between high intratumoral CD45RO (+) TIL infiltration and favorable prognosis. Conclusion: A sufficient degree of infiltration of stromal CD4 (+) TIL subsets is required for intratumoral CD45RO (+) TILs to exert toxicity against cancer cells. This highlights the significance of stromal immune reactions in achieving effective cytotoxic immune responses in the intratumoral area and demonstrates the critical role of the spatial distribution pattern of TILs in exerting their functions.