To Remember or to Forget: The Role of Good and Bad Memories in Adoptive T Cell Therapy for Tumors: Frontiers in Immunology

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The generation of immunological memory is a hallmark of adaptive immunity by which the immune system “remembers” a previous encounter with an antigen expressed by pathogens, tumors, or normal tissues; and, upon secondary encounters, mounts faster and more effective recall responses. The establishment of T cell memory is influenced by both cell-intrinsic and cell-extrinsic factors, including genetic, epigenetic and environmental triggers. Our current knowledge of the mechanisms involved in memory T cell differentiation has instructed new opportunities to engineer T cells with enhanced anti-tumor activity. The development of adoptive T cell therapy has emerged as a powerful approach to cure a subset of patients with advanced cancers. Efficacy of this approach often requires long-term persistence of transferred T cell products, which can vary according to their origin and manufacturing conditions. Host preconditioning and post-transfer supporting strategies have shown to promote their engraftment and survival by limiting the competition with a hostile tumor microenvironment and between pre-existing immune cell subsets. Although in the general view pre-existing memory can confer a selective advantage to adoptive T cell therapy, here we propose that also “bad memories”—in the form of antigen-experienced T cell subsets—co-evolve with consequences on newly transferred lymphocytes. In this review, we will first provide an overview of selected features of memory T cell subsets and, then, discuss their putative implications for adoptive T cell therapy. © Copyright © 2020 Mondino and Manzo.
Original languageEnglish
JournalFront. Immunol.
Publication statusPublished - 2020


  • adoptive T cell immunotherapy of cancer
  • competition
  • memory
  • T cell
  • tumor immunity
  • adaptive immunity
  • antineoplastic activity
  • cancer immunotherapy
  • carcinogenesis
  • CD4+ T lymphocyte
  • CD8+ T lymphocyte
  • cell differentiation
  • cell proliferation
  • cell transfer
  • clinical outcome
  • cytokine production
  • DNA damage
  • glycolysis
  • immune response
  • immune system
  • immunogenicity
  • immunology
  • innate immunity
  • intestine flora
  • knowledge
  • malignant neoplasm
  • mitochondrial biogenesis
  • mitochondrial respiration
  • overall survival
  • regulatory T lymphocyte
  • Review
  • signal transduction
  • T lymphocyte
  • tumor growth
  • tumor microenvironment
  • vaccination


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