Interleukin-7 and immune reconstitution in cancer patients: a new paradigm for dramatically increasing overall...

Although great effort is being expended in the development of cancer immunotherapies, it is surprising that global lymphopenia and its various dimensions are not being systematically assessed in cancer patients. The incident pathologies associated with various immunosuppressed conditions such as those found in HIV infection have taught us that measuring various T cell populations including CD4 provides the clinician with a reliable measure for gauging the risk of cancer and opportunistic infections. Importantly, recent data emphasize the key link between lymphocyte T cell counts and overall survival in cancer patients receiving chemotherapy. Treatment of immunocompromised patients with interleukin-7 (IL-7), a critical growth and homeostatic factor for T cells, has been shown to produce a compelling profile of T cell reconstitution. The clinical results of this investigational therapy confirm data obtained from numerous preclinical studies and demonstrate the long-term stability of this immune reconstitution, not only on CD4 but also on CD8 T cells, involving recent thymic emigrants as well as naive, memory, and central memory T cells. Furthermore, IL-7 therapy also contributes to restoration of a broadened diversity of the T cell repertoire as well as to migration of these cells to lymph nodes and tissues. All these properties support the initiation of new clinical studies aimed at reconstituting the immune system of cancer patients before or immediately after chemotherapy in order to demonstrate a potentially profound increase in overall survival.