The impact of preoperative treatments on the immune environment of rectal cancer

To improve local disease control, the use of preoperative radiotherapy either alone or combined with chemotherapy has become standard practice in rectal cancer, but it is unclear how these treatments modify the antitumoral immune response. We aimed to evaluate tumor histopathologic features and the prognostic effect of host immune response in rectal cancer with variable treatment modalities. Ninety-five rectal cancers with short-course radiotherapy (SRT), 97 with long-course chemoradiotherapy (CRT), and 154 without preoperative treatments, were evaluated for histopathologic features including Crohn's-like reaction (CLR). CD3+ and CD8+ immunohistochemistry and tumor cells were analyzed from tumor tissue microarray samples to calculate T-cell densities and G-cross function values to estimate cancer cell-T-cell co-localization (proximity score). We found that lymphocyte densities were diminished after SRT, but CLR was scarcer after CRT. Proximity score and CLR density were prognostic for survival in cancer without preoperative treatments and could be combined into an enhanced prognostic score (immune grade). In the irradiated tumors, CLR density remained prognostic while the impact of T-cell infiltration was insufficient alone. In multivariable analysis, the immune grade proved to be an independent prognostic factor for survival. In conclusion, the immune contexture of rectal cancer harbors prognostic significance even after preoperative radiotherapy.