The anti-tumour effect of CD8+ infiltration is associated with Human Leukocyte Antigen Class I expression and tumour proliferation in colorectal cancer

Purpose: The host inflammatory response is an important determinant of cancer outcome, however, the factor/s that regulate this response remains unclear. We aimed to determine if Human Leukocyte Antigen (HLA) class I and tumour cell proliferation are associated with CD8+ infiltration and survival in patients undergoing potentially curative resection for colorectal cancer. Methods: HLA class I expression (W6/32 and B2-microglobulin) and tumour proliferation index (Ki67) were quantified using immunohistochemistry on tissue micro arrays (TMA). The local inflammatory response at the invasive margin was assessed using the Klintrup-Makinen (K-M) score and CD8+ infiltration was assessed at the invasive margin (mCD8+), stroma (sCD8+) and cancer cell nests (cCD8+). Results: Preserved HLA class I expression was associated with lower Dukes stage (p=0.032), lower T stage (p=0.040) and higher cCD8+ (p=0.003). High Ki67 was associated with a good K-M score (p<0.001), higher mCD8+ (p=0.033), higher sCD8+ (p=0.025) and higher cCD8+ (p<0.001). On binary logistical regression analysis both preserved HLA class I expression (HR 1.99 95%CI (1.13-3.51),p=0.012) and high Ki67 (HR 2.63 95%CI (1.08-6.38),p=0.033) were independently associated with higher CD8+ infiltration within the cancer cell nests. On multivariate survival analysis, preserved HLA class I expression was associated with disease free (HR 0.47 95%CI (0.25-0.89),p=0.020) and cancer specific survival (HR 0.52 95%CI (0.28-0.97),p=0.038). Conclusion: This study suggests that a pronounced local inflammatory response is independently associated with both, HLA class I expression and tumour proliferation.