TY - JOUR
T1 - Hallmarks of Resistance to Immune-Checkpoint Inhibitors
AU - Karasarides, Maria
AU - Cogdill, Alexandria P.
AU - Robbins, Paul B.
AU - Bowden, Michaela
AU - Burton, Elizabeth M.
AU - Butterfield, Lisa H.
AU - Cesano, Alessandra
AU - Hammer, Christian
AU - Haymaker, Cara L.
AU - Horak, Christine E.
AU - McGee, Heather M.
AU - Monette, Anne
AU - Rudqvist, Nils Petter
AU - Spencer, Christine N.
AU - Sweis, Randy F.
AU - Vincent, Benjamin G.
AU - Wennerberg, Erik
AU - Yuan, Jianda
AU - Zappasodi, Roberta
AU - Hubbard Lucey, Vanessa M.
AU - Wells, Daniel K.
AU - LaVallee, Theresa
N1 - Publisher Copyright:
© 2022 The Authors.
PY - 2022/4
Y1 - 2022/4
N2 - Immune-checkpoint inhibitors (ICI), although revolutionary in improving long-term survival outcomes, are mostly effective in patients with immune-responsive tumors. Most patients with cancer either do not respond to ICIs at all or experience disease progression after an initial period of response. Treatment resistance to ICIs remains a major challenge and defines the biggest unmet medical need in oncology worldwide. In a collaborative workshop, thought leaders from academic, bio-pharma, and nonprofit sectors convened to outline a resistance framework to support and guide future immune-resistance research. Here, we explore the initial part of our effort by collating seminal discoveries through the lens of known biological processes. We highlight eight biological processes and refer to them as immune resistance nodes. We examine the seminal discoveries that define each immune resistance node and pose critical questions, which, if answered, would greatly expand our notion of immune resistance. Ultimately, the expansion and application of this work calls for the integration of multiomic high-dimensional analyses from patient-level data to produce a map of resistance phenotypes that can be utilized to guide effective drug development and improved patient outcomes.
AB - Immune-checkpoint inhibitors (ICI), although revolutionary in improving long-term survival outcomes, are mostly effective in patients with immune-responsive tumors. Most patients with cancer either do not respond to ICIs at all or experience disease progression after an initial period of response. Treatment resistance to ICIs remains a major challenge and defines the biggest unmet medical need in oncology worldwide. In a collaborative workshop, thought leaders from academic, bio-pharma, and nonprofit sectors convened to outline a resistance framework to support and guide future immune-resistance research. Here, we explore the initial part of our effort by collating seminal discoveries through the lens of known biological processes. We highlight eight biological processes and refer to them as immune resistance nodes. We examine the seminal discoveries that define each immune resistance node and pose critical questions, which, if answered, would greatly expand our notion of immune resistance. Ultimately, the expansion and application of this work calls for the integration of multiomic high-dimensional analyses from patient-level data to produce a map of resistance phenotypes that can be utilized to guide effective drug development and improved patient outcomes.
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U2 - 10.1158/2326-6066.CIR-20-0586
DO - 10.1158/2326-6066.CIR-20-0586
M3 - Article
C2 - 35362046
AN - SCOPUS:85127456459
SN - 2326-6066
VL - 10
SP - 372
EP - 383
JO - Cancer Immunology Research
JF - Cancer Immunology Research
IS - 4
ER -