TY - JOUR
T1 - Strategies to Overcome Failures in T-Cell Immunotherapies by Targeting PI3K-δ and –γ
AU - Chandrasekaran, Sanjay
AU - Funk, Christopher Ronald
AU - Kleber, Troy
AU - Paulos, Chrystal M.
AU - Shanmugam, Mala
AU - Waller, Edmund K.
N1 - Publisher Copyright:
© Copyright © 2021 Chandrasekaran, Funk, Kleber, Paulos, Shanmugam and Waller.
PY - 2021/8/26
Y1 - 2021/8/26
N2 - PI3K-δ and PI3K-γ are critical regulators of T-cell differentiation, senescence, and metabolism. PI3K-δ and PI3K-γ signaling can contribute to T-cell inhibition via intrinsic mechanisms and regulation of suppressor cell populations, including regulatory T-cells and myeloid derived suppressor cells in the tumor. We examine an exciting new role for using selective inhibitors of the PI3K δ- and γ-isoforms as modulators of T-cell phenotype and function in immunotherapy. Herein we review the current literature on the implications of PI3K-δ and -γ inhibition in T-cell biology, discuss existing challenges in adoptive T-cell therapies and checkpoint blockade inhibitors, and highlight ongoing efforts and future directions to incorporate PI3K-δ and PI3K-γ as synergistic T-cell modulators in immunotherapy.
AB - PI3K-δ and PI3K-γ are critical regulators of T-cell differentiation, senescence, and metabolism. PI3K-δ and PI3K-γ signaling can contribute to T-cell inhibition via intrinsic mechanisms and regulation of suppressor cell populations, including regulatory T-cells and myeloid derived suppressor cells in the tumor. We examine an exciting new role for using selective inhibitors of the PI3K δ- and γ-isoforms as modulators of T-cell phenotype and function in immunotherapy. Herein we review the current literature on the implications of PI3K-δ and -γ inhibition in T-cell biology, discuss existing challenges in adoptive T-cell therapies and checkpoint blockade inhibitors, and highlight ongoing efforts and future directions to incorporate PI3K-δ and PI3K-γ as synergistic T-cell modulators in immunotherapy.
KW - CAR T cancer therapy
KW - PI3K delta
KW - PI3K gamma
KW - T cell differentiation
KW - TIL (tumor infiltrating lymphocytes)
KW - adoptive cell immunotherapy
KW - immune checkpoint inhibition (ICI)
UR - http://www.scopus.com/inward/record.url?scp=85114593592&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85114593592&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2021.718621
DO - 10.3389/fimmu.2021.718621
M3 - Review article
C2 - 34512641
AN - SCOPUS:85114593592
SN - 1664-3224
VL - 12
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 718621
ER -