The Song of the Cell: An Exploration of Medicine and the New Human

by Siddhartha Mukherjee

Why, how—why, why, why, how, how—can a cancer cell circumvent T cells designed to recognize and kill it? This question haunts immunotherapy today. Something about a solid tumor—perhaps the environment that it has created around itself—can circumvent and inhibit even the most potent reactivation of T cells. What is that “something”? The most solid evidence, and this is not a play on words, is that the immune attack on a cancer can occur only if a fully active lymphoid organ, containing neutrophils, macrophages, helper T cells, killer T cells, and an organized cellular structure, can be formed within a solid tumor. This secondary lymphoid organ (SLO) is like a lymph node that is usually formed when T cells attack a virus or a pathogen, except in this case, it is organized against a tumor. Tumors that do not enable the formation of such SLOs are resistant to immunotherapy, while those that do form them are generally sensitive. But that’s a correlation. The cause-and-effect relationships, and the mechanisms that enable or disable the formation of such SLOs, have yet to be uncovered. Once we understand them, a new generation of immunotherapeutic drugs, or combinations, can be unleashed on cancer cells.