Adaptive Resistance to Cancer Immunotherapy

  • A. J. Robert McGray
  • Jonathan Bramson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1036)


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.


Adaptive resistance Immune suppression T Lymphocyte Tumor microenvironment Checkpoint blockade IFN-γ 


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Center for ImmunotherapyRoswell Park Cancer InstituteBuffaloUSA
  2. 2.Department of Pathology and Molecular MedicineMcMaster UniversityHamiltonCanada

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