TY - JOUR
T1 - Neoadjuvant checkpoint blockade for cancer immunotherapy
AU - Topalian, Suzanne L.
AU - Taube, Janis M.
AU - Pardoll, Drew M.
N1 - Funding Information:
We gratefully acknowledge research support from NCI R01 CA142779 (to S.L.T., J.M.T., and D.M.P.), the Cancer Research Institute/Stand Up To Cancer-Immunology Translational Cancer Research Grant AACR-DT1012 (to D.M.P.), Bristol-Myers Squibb (S.L.T., J.M.T., and D.M.P.), the Barney Family Foundation (S.L.T.), Moving for Melanoma of Delaware (S.L.T.), the Laverna Hahn Charitable Trust (S.L.T.), the Melanoma Research Alliance (J.M.T.), the Harry J. Lloyd Charitable Trust (J.M.T.), the Emerson Collective Foundation (J.M.T.), the Mark Foundation for Cancer Research (J.M.T. and D.M.P.), and the Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy (S.L.T., J.M.T., and D.M.P.).
Publisher Copyright:
Copyright © 2020 The Authors,
PY - 2020/1/31
Y1 - 2020/1/31
N2 - Cancer immunotherapies that target the programmed cell death 1 (PD-1):programmed death-ligand 1 (PD-L1) immune checkpoint pathway have ushered in the modern oncology era. Drugs that block PD-1 or PD-L1 facilitate endogenous antitumor immunity and, because of their broad activity spectrum, have been regarded as a common denominator for cancer therapy. Nevertheless, many advanced tumors demonstrate de novo or acquired treatment resistance, and ongoing research efforts are focused on improving patient outcomes. Using anti–PD-1 or anti–PD-L1 treatment against earlier stages of cancer is hypothesized to be one such solution. This Review focuses on the development of neoadjuvant (presurgical) immunotherapy in the era of PD-1 pathway blockade, highlighting particular considerations for biological mechanisms, clinical trial design, and pathologic response assessments. Findings from neoadjuvant immunotherapy studies may reveal pathways, mechanisms, and molecules that can be cotargeted in new treatment combinations to increase anti–PD-1 and anti–PD-L1 efficacy.
AB - Cancer immunotherapies that target the programmed cell death 1 (PD-1):programmed death-ligand 1 (PD-L1) immune checkpoint pathway have ushered in the modern oncology era. Drugs that block PD-1 or PD-L1 facilitate endogenous antitumor immunity and, because of their broad activity spectrum, have been regarded as a common denominator for cancer therapy. Nevertheless, many advanced tumors demonstrate de novo or acquired treatment resistance, and ongoing research efforts are focused on improving patient outcomes. Using anti–PD-1 or anti–PD-L1 treatment against earlier stages of cancer is hypothesized to be one such solution. This Review focuses on the development of neoadjuvant (presurgical) immunotherapy in the era of PD-1 pathway blockade, highlighting particular considerations for biological mechanisms, clinical trial design, and pathologic response assessments. Findings from neoadjuvant immunotherapy studies may reveal pathways, mechanisms, and molecules that can be cotargeted in new treatment combinations to increase anti–PD-1 and anti–PD-L1 efficacy.
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U2 - 10.1126/science.aax0182
DO - 10.1126/science.aax0182
M3 - Review article
C2 - 32001626
AN - SCOPUS:85078710390
SN - 0036-8075
VL - 367
JO - Science
JF - Science
IS - 6477
M1 - eaax0182
ER -