Combining immunotherapy with chemotherapy to treat cancer

Extract: Cytotoxic chemotherapy remains one of the most widely available treatment options for cancer. Unfortunately, the efficacy of chemotherapy is limited and, for solid tumors in particular, cures are rarely achieved. Immunotherapy is a more experimental treatment method, aimed at mobilizing the body's immune cells to attack tumor cells, but it is also rarely curative. Few studies have investigated the options for combining chemotherapy and immunotherapy, largely because the two forms of treatment are considered to be antagonistic. Two assumptions have contributed to this view. First, most chemotherapies kill target cells by triggering a process of programmed cell death, or apoptosis, and this mode of cell death has been regarded as non-stimulatory or tolerogenic (induces tolerance). Thus, apoptosis-inducing chemotherapy would be expected to induce a state of non-responsiveness in the cytotoxic T lymphocytes that could otherwise potentially destroy tumor cells. Second, lymphocyte depletion (lymphopenia) is a common side effect of many anti-cancer drugs, and this too has been assumed to be detrimental to any potential immune response. However, recent advances in our thinking on immune regulation now challenge both of these assumptions. Here, we will review how recent data support the case for combining chemotherapy and immunotherapy in cancer treatment.