HLA-A2 antigen status predicts metastasis and response to immunotherapy in gastric cancer

Our previous studies have shown that HLA-DR4 and -B52 antigens are associated with an increased risk of lymph node metastasis in patients with gastric cancer. We hypothesized that a putative HLA antigen, correlated with a low risk of lymph node metastasis, may also be correlated with the response to anticancer therapy. The microcytotoxicity assay was used to examine 49 HLA antigens of the A, B, C, DR, and DQ loci, and the association between HLA class I and II antigen status and lymph node metastasis in 847 patients with gastric cancer as well as the response to the therapy in 739 patients were analyzed. HLA-A2 antigen was significantly associated with a low risk of lymph node metastasis in patients with T2-T4 advanced cancer [58.8% compared to 37.0% in patients with lymph node metastasis; corrected P, Pc (98), = 0.011], especially in those with moderately differentiated adenocarcinoma [71.0% compared to 26.4% in patients with lymph node metastasis, Pc (294) = 0.00294] and with a better response to post-operative immunotherapy using protein-bound polysaccharide K (PSK), a nonspecific immunomodulator, than to chemotherapy. HLA alleles may be associated with resistance or susceptibility to lymph node metastasis and HLA-A2 antigen may be a useful predictor of the response to PSK. The data suggest that the predictive power of this HLA antigen may prove useful in the selection of anticancer therapy.