Tumor-infiltrating lymphocytes in patients with metastatic melanoma receiving chemoimmunotherapy

Biopsies from 12 patients with progressive metastatic melanoma were excised during chemoimmunotherapy to evaluate and characterize the local immune response in situ in the metastases. These findings were compared with the distribution of lymphocyte subsets in the peripheral blood and correlated with the clinical data. The biopsy specimens were prepared for microscopic procedures, and the fields for analyses were chosen to involve a section of both the stroma and the tumor area. The number of each lymphocyte subset was calculated and compared with the number of melanoma cells in the field, allowing quantitative characterization of the immune reaction in different samples. Comparison of the lymphocyte subsets of peripheral blood and metastatic lesions revealed equal relative amounts of CD4(+) (helper) and CD8(+) (suppressor/cytotoxic) cells in both tissues, but 10- to 20-fold fewer CD56(+) (natural killer, NK) cells, and a total absence of CD20(+) (B) cells in the metastatic lesions. The prognosis of patients was viewed at different stages of the disease. The median survival from the primary diagnosis of patients with a tumor CD4(+)/CD8(+) ratio above the median was 4.4 years compared with 2.4 years for those with a ratio below the median (Logrank, p = 0.02). In the multivariate analysis, the only statistically significant prognostic factors were the CD4(+)/CD8(+) ratio of the tumor (p = 0.010) and of the peripheral blood (p = 0.020). Monitoring of CD4(+) and CD8(+) cells may thus provide valuable information about the state of host defense, with a high CD4(+)/CD8(+) ratio indicating more favorable prognosis.