Prognostic value of HLA class I expression in patients with colorectal cancer.

BACKGROUND: Prognostic factors are useful for determination of the therapeutic strategy and follow-up examination after curative operation in cancer treatment. The immunological state of the host can influence the prognosis for cancer patients as well as the features of the cancer. Human lymphocyte antigen (HLA) class I molecules have a central role in the anti-cancer immune system. Therefore, we focused on the HLA class I expression level in cancer cells to investigate its prognostic value in patients with colorectal cancer. METHODS: We reviewed the clinical pathology archives of 97 consecutive patients with stage II colorectal cancer who underwent curative operation at the Sapporo Medical University, Japan, from February 1994 to January 2005. Fifty-six high-risk patients had adjuvant chemotherapy. The cancer cell membrane immunoreactivity level for HLA class I expressed by EMR8-5 was classified into three categories (positive, dull, and negative). In this study, the cases were divided into two groups: "positive" and "dull/negative". HLA class I expression level and clinicopathological parameters were evaluated with the Pearson χ (2) test. Survival analysis was assessed by the Kaplan-Meier methods, and the differences between survival curves were analyzed using the log-rank test. RESULTS: Immunohistochemical study of HLA class I revealed the following. There were 51 cases that were positive, 40 were dull, and six negative. The HLA class I expression level had no significant correlation with other clinicopathological parameters, except for gender. Univariate and multivariate analyses related to disease-free survival (DFS) revealed that tumor location, HLA expression level, and venous invasion were significant independent prognostic factors (P < 0.05). The 5-year DFS rates in HLA class I positive group and in the dull/negative group were 89% and 70%, respectively. For high-risk patients with adjuvant chemotherapy, the 5-year DFS rates in the HLA class I positive group and in the dull/negative group were 84% and 68%, respectively. For low-risk patients without the chemotherapy, the 5-year DFS rates in the HLA class I positive group and in the dull/negative group were 100% and 71%, respectively. CONCLUSIONS: Our study concluded that the HLA class I expression level might be a very sensitive prognostic factor in colorectal cancer patients with stage II disease.

Heat shock proteins and immunity: application of hyperthermia for immunomodulation.

Heat shock proteins (HSPs) play an important role as 'endogenous danger signals' in the immune surveillance system. Extracellular HSPs released from damaged cells can stimulate professional antigen-presenting cells, followed by cytokine release and expression of cell surface molecules. In addition to such activity stimulating innate immunity, extracellular HSPs can promote the cross-presentation of HSP-bound peptide antigens to MHC class I molecules in dendritic cells, leading to efficient induction of antigen-specific cytotoxic T-lymphocytes. The roles of HSPs stimulating both innate immunity and adaptive immunity can explain at least in part the molecular mechanism by which thermal stress bolsters the host immune system. In the present review, we present novel aspects of the roles of HSPs in immunity and discuss the therapeutic application of hyperthermia for immunomodulation.