This book chapter by McGray and Bramson in Tumor Immune Microenvironment in Cancer Progression and Cancer Therapy (Springer; ed - Kalinsky) reviews current theories on how tumors escape immune surveillance, evolve in response to ongoing immune attacks, and cultivate an immunosuppressive microenvironment. They discuss the role that adaptive resistance plays in immunotherapy, and some strategies to overcome it. The full book contains multiple additional chapters relevant to the field of cancer immunotherapy.

Immunosuppressive mechanisms within the tumor microenvironment have emerged as a major impediment to cancer immunotherapy. While a broad range of secreted factors, receptors/ligands, and cell populations have been described that contribute to the immunosuppression, the involvement of these processes in immune evasion by tumors is typically considered to be an intrinsic property of the tumor. Evidence is now emerging that the processes underlying immune suppression within the tumor are, in fact, triggered by immune attack and reflect a dynamic interplay between the tumor and the host's immune system. The term adaptive resistance has been coined to describe the induction of immune suppressive pathways in the tumor following active attack on the tumor. Adaptive resistance is a scalable process where the magnitude of immune suppression matches the magnitude of the immune attack; the net balance between suppression and attack determines the durability of the anti-tumor response and tumor outcome. In this chapter, we will examine the data supporting adaptive resistance and the opposing roles of T cells in simultaneously promoting both anti-tumor immunity and immune suppression within the tumor microenvironment. The clinical implications of adaptive resistance in the design and application of immunotherapeutic strategies is also discussed.

Author Info: (1) Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY, USA. bobmcgray@gmail.com. (2) Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.

Author Info: (1) Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY, USA. bobmcgray@gmail.com. (2) Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.

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