Does endogenous immune response determine the outcome of surgical therapy for metastatic melanoma?

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Abstract
Although the presence of tumor cells in the blood of patients with metastatic melanoma suggests widely disseminated disease many of these patients enjoy prolonged survival or cure after surgical resection. Our previous study of adjuvant vaccine therapy after complete resection of metastatic melanoma revealed a strong correlation between postoperative survival and elevated antibody titers to a 90-kDa tumor-associated antigen (TA90) expressed by melanoma cells of the vaccine. We hypothesized a similar correlation between postoperative survival and endogenous anti-TA90 antibody titers induced by the patient’s melanoma in the absence of postoperative adjuvant immunotherapy. From 1970 to 1996, 64 patients underwent complete resection of distant melanoma metastases and did not receive postoperative adjuvant immunotherapy. Serum collected within 4 months after surgery was tested in a coded and blinded fashion for anti-TA90 IgG and IgM by enzyme-linked immunosorbent assay, and for total IgG and IgM (controls) by radial immunodiffusion. Median follow-up for the study population was 19 months (range, 3–147 months). There was no significant correlation between anti-TA90 IgG titer and total IgG level (P=.4785), or between anti-TA90 IgM and total IgM (P=.0989). Univariate analysis showed that postoperative anti-TA90 IgM titer as a continuous variable was significantly associated with overall survival (OS); i.e, the higher the anti-TA90 IgM titer, the longer the OS. Using an established cutoff titer of 800, median OS was 42 months for patients with high anti-TA90 IgM titer (n=28) vs. 9 months for patients with low titers (n=36) (P=.0001). There was no significant correlation between total IgG/IgM and survival (P=.4107 and .4044, respectively). Multivariate, analysis identified anti-TA90 IgM as the most significant independent variable influencing OS after complete resection of distant melanoma metastases (P-.0001). We conclude that the endogenous immune response to metastatic melanoma determines the outcome after surgical therapy. Enhancement of this specific immune response may prolong the survival of patients with distant melanoma metastases.