Impact of HTLV-1 infection on clinicopathological characteristics and tumour immune microenvironment in colorectal cancer

Recent advances in anti-cancer therapy have indicated the significance of the tumour immune microenvironment in tumour progression and resistance to anti-cancer therapy. This study investigated primary colorectal cancer (CRC) tissues resected from 180 cases in a single institute in a region highly endemic for human T-cell leukaemia virus type 1 (HTLV-1) carriers. Among those 180 cases, 35 HTLV-1 carriers were identified. CRC patients who were HTLV-1 carriers were significantly older (mean age: 76.9 vs. 72.7 years, P = 0.0341), with a lower incidence of lymph node metastases (pN0: 91% vs. 65%, P = 0.0085), and lower tumour stages (stage III or IV: 11% vs. 36%, P = 0.0117) compared to non-carriers. HTLV-1 carriers tended to show a lower incidence of relapse, although the difference was not significant (P = 0.2272). The density of forkhead box P3-positive regulatory T cells (Tregs) was significantly higher in HTLV-1 carriers (median density: 132 vs. 89 cells/mm², P = 0.0051). In situ hybridisation showed cells positive for HTLV-1 basic leucine zipper factor, likely representing lymphocytes located in stroma around the cancer nest. Our findings indicate that lymph node metastasis was significantly suppressed in CRC patients infected with HTLV-1. Since HTLV-1 infection reportedly impairs the immunosuppressive functions of Tregs, anti-cancer immune responses are potentially enhanced in CRC patients who are HTLV-1 carriers.