Abstract
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.
Highlights
Reviewed by: Karl Kai McKinstry, University of Central Florida, United States Roslyn Kemp, University of Otago, New Zealand
The degree of heterogeneity within a T cell pool depends on the integration of signals from the T cell receptor (TCR), co-stimulatory molecules, cytokines and nutrients, and on the relative cell fitness within an environment competing for the same resources
The concept of immunological memory foresees that pre-existing memory T cells would be beneficial for protection against reinfection with the same pathogens, because Ag-specific memory T cells would be numerically increased when compared to endogenous ones, have widened anatomical distribution, and respond more quickly, conferring rapid clearance of the infectious agent
Summary
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. The adoption of ACT envisages several steps: [1] generation of T cell products, [2] conditioning of the host, [3] T-cell transfer, and [4] post-transfer cell support Each of these steps can have a critical impact on ACT therapeutic efficacy, and vary according to infused T cells’ TM features, and simultaneously shape the immune landscape of the host.
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