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Fueling Cancer Immunotherapy With Common Gamma Chain Cytokines
oleh: Connor J. Dwyer, Connor J. Dwyer, Hannah M. Knochelmann, Hannah M. Knochelmann, Aubrey S. Smith, Aubrey S. Smith, Megan M. Wyatt, Megan M. Wyatt, Guillermo O. Rangel Rivera, Guillermo O. Rangel Rivera, Dimitrios C. Arhontoulis, Dimitrios C. Arhontoulis, Eric Bartee, Zihai Li, Mark P. Rubinstein, Mark P. Rubinstein, Chrystal M. Paulos, Chrystal M. Paulos
Format: | Article |
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Diterbitkan: | Frontiers Media S.A. 2019-02-01 |
Deskripsi
Adoptive T cell transfer therapy (ACT) using tumor infiltrating lymphocytes or lymphocytes redirected with antigen receptors (CAR or TCR) has revolutionized the field of cancer immunotherapy. Although CAR T cell therapy mediates robust responses in patients with hematological malignancies, this approach has been less effective for treating patients with solid tumors. Additionally, toxicities post T cell infusion highlight the need for safer ACT protocols. Current protocols traditionally expand T lymphocytes isolated from patient tumors or from peripheral blood to large magnitudes in the presence of high dose IL-2 prior to infusion. Unfortunately, this expansion protocol differentiates T cells to a full effector or terminal phenotype in vitro, consequently reducing their long-term survival and antitumor effectiveness in vivo. Post-infusion, T cells face further obstacles limiting their persistence and function within the suppressive tumor microenvironment. Therapeutic manipulation of T cells with common γ chain cytokines, which are critical growth factors for T cells, may be the key to bypass such immunological hurdles. Herein, we discuss the primary functions of the common γ chain cytokines impacting T cell survival and memory and then elaborate on how these distinct cytokines have been used to augment T cell-based cancer immunotherapy.