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Adoptive immunotherapy for human cancers: Flagmen signal first “open road” then “roadblocks.” A narrative synopsis

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Book cover Atlas Effectors of Anti-Tumor Immunity

Abstract

There was overwhelming evidence documented in vitro in the early 1970s for lymphocyte-mediated cytotoxicity to autologous cancer cells. Cancer-bearing patients circulated small compact lymphocytes in their blood that promptly killed their tumor cells in vitro. These lymphocytes were identified later as CD8+ immune T cells. Tumor cells were killed by cytoplasmic lysis with perforins and granzymes, or by nuclear clumping by Fas ligand and related ligands. With the discovery of T cell growth factor (interleukin-2), the road for lymphocyte therapy of human cancers appeared wide open. Then emerged the “large granular lymphocytes”. These cells occurred not only in patients with cancer, but in healthy cancer-free individuals. The author of this article served as “negative (healthy) control” in the cytotoxicity assays in the late 1960s and early 1970s. Some project site visitors of the National Cancer Institute could not comprehend that “immune reactions could exist without pre-immunization” and referred to the phenomenon as an “in vitro artifact” (worse than that: they canceled grant support for its study). It was years later, that first in mice and then in human patients the “large granular lymphocytes” were recognized as natural killer cells. Then emerged the “suppressor/regulatory T cells” (TREG). This lymphocyte population is responsible for curtailing autoimmune reactions against “self ”. Tumor cells masquerading as “self ” are protected by TREG against cytotoxicity executed by immune T cells, and even by NK cells. Adoptive immune lymphocyte therapy of human cancer will be effectively resolved when technology develops for the neutralization of the TREG population.

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Authors and Affiliations

  1. Department of Medical Microbiology & Immunology, St. Joseph‘s Hospital‘s Cancer Institute Affiliated with the H. L. Moffitt Comprehensive Cancer Center at the University of South Florida College of Medicine, Tampa, FL, USA

    Joseph G. Sinkovics

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  1. Joseph G. Sinkovics
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  1. Laboratory of Cell Immunity NN Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoe shosse 24, Moscow, Russia 115478

    Mikhail V. Kiselevsky

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Sinkovics, J.G. (2008). Adoptive immunotherapy for human cancers: Flagmen signal first “open road” then “roadblocks.” A narrative synopsis. In: Kiselevsky, M.V. (eds) Atlas Effectors of Anti-Tumor Immunity. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6931-4_1

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