Lung colonization and metastasis by disseminated b16 melanoma cells: H‐2 associated control at the level of the host and the tumor cell

We have studied the experimental metastasis of H‐2 + and H‐2 − melanoma sublines in H‐2 b/b and H‐2 a/b hosts by enumerating pulmonary colonies 20–50 days after i.v. inoculation of tumor cells. In H‐2 b/b hosts, the H‐2 + „B 16‐S” cells gave rise to a moderate number of metastatic colonies (mean: 6.3 ± 6). The „BL 16‐L” sublines that had lost the expression of MHC class I antigens, according to FACS‐analysis and quantitative absorption tests, gave no metastases under the same conditions. Pretreatment of the H‐2 + met + B 16‐S with interferons (beta or alpha + beta) increased their H‐2 antigen expression and the number of metastatic colonies (mean: 25 ± 16). Interferon pretreatment of B16‐L cells partially restored their H‐2 b expression and induced them to form a small number of metastatic colonies. The reduction in pulmonary colonization by the H‐2 negative B16‐L cells could be attributed to their rapid elimination by natural killer cells, already observed within 24 hr of inoculation of radiolabelled cells. H‐2 − B16‐L cells were more susceptible than H‐ 2+ B16‐S cells to in vitro lysis by poly I:C‐treated splenocytes, and they acquired full metastatic abilities if the hosts were treated with anti‐asialo GM‐I serum. In H‐2 a/b heterozygous hosts, the H‐2 + B16‐S cells also failed to metastasize. Reduced pulmonary colonization was evident by 24 hr after injection in comparison with H‐2 b/b hosts, and could be reversed by anti‐asialo GM‐I treatment of the hosts. In vitro , H‐2 a/b splenocytes were more cytotoxic to the B16 cells than syngeneic effectors. The results are discussed in relation to a recent hypothesis on a surveillance mechanism for elimination of cells on the basis of their lack (or insufficient expression) of host MHC genes.