Introduction: Immunity of colitis-associated colorectal cancer (CAC) differs fundamentally from that of the sporadic form. The aim of this study was to evaluate whether this difference could potentiate the efficacy of immune-checkpoint inhibitor anti-PD1 against CAC.
Methods: CAC tumorigenesis was induced by azoxymethane (AOM) followed by three cycles of dextran sodium sulfate (DSS) in mice. Two weeks after the end of DSS, mice were treated with anti-PD1 antibody (n=9) or with isotype antibody (n=9). The severity of clinical and histological colitis, tumor counts, and infiltration of CD8+ T-lymphocytes and neutrophils were compared.
Results: The anti-PD1 antibody did not aggravate the colitis as exemplified by the absence of differences in weight loss (p=0.424) and in the standardized pathological scores (p=1.000) compared to those of the control. On macroscopic examination, the median number of tumors was 24.0 [21.5/31.0] in treated mice and 17.0 [4.0/23.5] in controls (p=0.037). The percentage of tumor tissue within the entire colonic epithelium was significantly higher in treated mice (33.1% [27.2/39.0]) than in controls (15.3% [8.1/25.0]) (p=0.003). The intra-tumoral CD8+ T-lymphocyte density was similar between the two groups (p=0.546). In contrast, CD8+ T-lymphocyte density was significantly higher in non-tumor colonic epithelium in treated mice than in controls (p=0.019). Regarding innate immunity, neutrophil density was similar within the tumors (p=0.864) and augmented in non-tumor colonic epithelium in treated mice compared with controls (p=0.012).
Conclusion: Unexpectedly, checkpoint inhibitor anti-PD1 treatment of CAC stimulates tumor proliferation without flaring-up the colitis.