Different immune correlates associated with tumor progression and regression: Implications for prevention and treatment of cancer

Observations show that humans and animals respond immunologically to most cancers. Why does the immune system then fail to control cancer? We argue from the literature that there is a commonality in the regulation of responses against most murine tumors, and that a major mechanism of escape may be deviation of an effective Th1, cytotoxic T lymphocyte response to a less effective response with a Th2 component. We examined this hypothesis with two well-studied murine tumors. We found, following primary tumor implantation, that resistance correlates with Th1 responses and IgG2a antibody production and progression with mixed Th1/Th2 responses and production of IgG1 and IgG2a antibodies. Resistance is associated with a modulation of the anti-tumor response towards the Th1 pole in both systems. We conclude that the immune responses against these two tumors are in accord with our hypothesis, and argue that this is likely to be true of many human and murine tumors. The correlation of IgG isotype of anti-tumor antibody with the Th1/Th2 nature of the anti-tumor response readily allows one to longitudinally monitor the changing nature of the anti-tumor response. We suggest that such monitoring can guide immunotherapy to maximize the effectiveness of the host's immune response against cancer.