HLA and TNF Studies in Preventive Oncology
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We have investigated whether HLA and its related genes such as the TNF gene act as predictive, prognostic factors or as indicators of bioresponse modification of the response to postoperative adjuvant therapy for the risk of lymph node metastasis in gastric and lung cancer patients.We found 3 interesting observations as follows from our own studies with the HLA serological test and TNF-DNA-PCR-RFLP method.(1) The 5-year survival rates for patients with HLA-B40 antigen who received chemotherapy plus PSK after gastrectomy and those with HLA B51 antigen who received chemotherapy alone after gastrectomy were 100% in both groups, whereas patients without HLA-B40 and patients with HLA-B51 who received chemotherapy plus PSK after gastrectomy had survival rates of 67.3% and 37.7%, respectively (P<0.05 and P<0.05 in log-rank test).(2) The HLA-B40 and HLA-Cw3 antigens were associated with a decreased risk of lymph node involvement, whereas HLA-A24 was associated with an increased risk of lymph node involvement in Japanese gastric cancer patients.(3) TNF B 10.5/10.5 gene may be a resistant factor for oncogenesis of lung cancer and may function as a prognostic factor. The mechanisms of the abovementioned observations are still not clear. There have been many studies concerning MHC and disease susceptibility in human and mice, but few studies on the positive association between HLA and/or HLA related gene and disease prognosis and treatment have recently been reported38-42).Other immunological factors such as, TCR, HLA restriction and cytokine production should be investigated in future studies. It is recognized and accepted that the TNM classification proposed by the International Union Against Cancer in 1987 is an important observation of prognosis and treatment in oncology.However, the TNM classification is directed to the tumor itself but not to the host.Therefore we would like to propose further establishment of additional factors in the TNM classification43) such as TNMH.H factor, which means host factors, may consist of these factors; 1) HLA typing, 2) HLA related genes, such as TNF B gene, 3) immunological responses and 4) others.In this chapter review including our preliminary studies, we presented 1) HLA update, 2) TNF B in lung cancer, 3) HLA in gastric cancer and finally propose a new concept, i. e., TNMH instead of TNM in future preventive oncology.ACKNOWLEDGMENT We thank Mr. K. Sato for HLA serology typing and Dr. F. KATO and Y. Hayata for providing blood samples from lung cancer patients in Tokyo Medical College.These studies were supported, in part, by a grant from the Smoking Research Foundation and by a Grant-in-Aid for Cancer Research (04-29) from the Ministry of Health and Welfare, Japan.
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