In a set of highly informative articles focused on immunologic memory published in Immunological Reviews, Reading et al. tackle the formation and loss of effective memory CD8+ cells and the unique impact of an evolving tumor microenvironment. Conversion of helpful, but transient, responses to checkpoint or adoptive T cell therapy into durable benefit depends critically on understanding and controlling the multiplicity of factors affecting CD8+ memory cell formation. Other notable topics reviewed include the role of cytokines and stroma, other immune cells, and metabolism.

The generation and maintenance of CD8(+) T cell memory is crucial to long-term host survival, yet the basic tenets of CD8(+) T cell immunity are still being established. Recent work has led to the discovery of tissue-resident memory cells and refined our understanding of the transcriptional and epigenetic basis of CD8(+) T cell differentiation and dysregulation. In parallel, the unprecedented clinical success of immunotherapy has galvanized an intense, global research effort to decipher and de-repress the anti-tumor response. However, the progress of immunotherapy is at a critical juncture, since the efficacy of immuno-oncology agents remains confined to a fraction of patients and often fails to provide durable benefit. Unlocking the potential of immunotherapy requires the design of strategies that both induce a potent effector response and reliably forge stable, functional memory T cell pools capable of protecting from recurrence or relapse. It is therefore essential that basic and emerging concepts of memory T cell biology are rapidly and faithfully transposed to advance therapeutic development in cancer immunotherapy. This review highlights seminal and recent reports in CD8(+) T cell memory and tumor immunology, and evaluates recent data from solid cancer specimens in the context of the key paradigms from preclinical models. We elucidate the potential significance of circulating effector cells poised downstream of neoantigen recognition and upstream of T cell dysfunction and propose that cells in this immunological 'sweet spot' may be key anti-tumor effectors.

Author Info: (1) Cancer Immunology Unit, University College London Cancer Institute, University College London, London, UK. Research Department of Haematology, University College London Cancer Institute, University College

Author Info: (1) Cancer Immunology Unit, University College London Cancer Institute, University College London, London, UK. Research Department of Haematology, University College London Cancer Institute, University College London, London, UK. (2) Laboratory of Gene Immunotherapy, Fundacion Ciencia & Vida, Santiago, Chile. (3) The Francis Crick Institute, London, UK. (4) Laboratory of Gene Immunotherapy, Fundacion Ciencia & Vida, Santiago, Chile. (5) Cancer Immunology Unit, University College London Cancer Institute, University College London, London, UK. Research Department of Haematology, University College London Cancer Institute, University College London, London, UK. (6) Cancer Immunology Unit, University College London Cancer Institute, University College London, London, UK. Research Department of Haematology, University College London Cancer Institute, University College London, London, UK.

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