Chapter 6

Anticancer Immunotherapy in Combination with Proapoptotic Therapy - Possible Therapeutic Strategies for Enhancement of Anticancer Immune Reactivity in Autologous Immunocompetent Cells and After Allogeneic Stem Cell Transplantation

Håkon Reikvam, Elisabeth Ersvær, Guro Kristin Melve, Astrid Olsnes Kittang, Bjørn Tore Gjertsen and Øystein Bruserud


Induction of immune responses against cancer-associated antigens is possible, but the optimal use of this strategy remains to be established and especially the combination of T cell therapy and new targeted therapeutic agents should be investigated. The design of future clinical studies has to consider several issues. Firstly, induction of anticancer T cell reactivity seems most effective in patients with low disease burden. Initial disease-reducing therapy including surgery, irradiation and conventional or new targeted chemotherapy should therefore be used, preferably through induction of immunogenic cancer cell death. Secondly, after the induction phase effector T cells will induce cancer cell apoptosis mainly through the intrinsic apoptosis-regulating pathway. The effect of this effector T cell function should be strengthened by administration of chemotherapy that mediates additional proapoptotic signalling through the external apoptosis-regulating pathway, inhibition of survival signalling or blocking of anti-apoptotic signalling. Thirdly, the status of the immune system has to be considered, including the postchemotherapy CD4+ T cell defect, the balance between proinflammatory and immunosuppressive T cell subsets (e.g. regulatory T cells versus Th17 cells), and immunoregulatory mesenchymal cells that can be detected within tumors. Immunotherapy should probably be initiated early after disease-reducing therapy when the cancer cell burden is lowest and a focus should then be to alter the balance in favour of proinflammatory T cell subsets. All these issues need to be considered in the design of future clinical studies combining chemotherapy and immunotherapy.

Total Pages: 172-206 (35)

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