TY - JOUR
T1 - Leveraging immune resistance archetypes in solid cancer to inform next-generation anticancer therapies
AU - Anderson, Kristin G.
AU - Braun, David A.
AU - Buqué, Aitziber
AU - Gitto, Sarah B.
AU - Guerriero, Jennifer L.
AU - Horton, Brendan
AU - Keenan, Bridget P.
AU - Kim, Teresa S.
AU - Overacre-Delgoffe, Abigail
AU - Ruella, Marco
AU - Triplett, Todd A.
AU - Veeranki, Omkara
AU - Verma, Vivek
AU - Zhang, Fan
N1 - Publisher Copyright:
© 2023 Open Heart
PY - 2023/6/30
Y1 - 2023/6/30
N2 - Anticancer immunotherapies, such as immune checkpoint inhibitors, bispecific antibodies, and chimeric antigen receptor T cells, have improved outcomes for patients with a variety of malignancies. However, most patients either do not initially respond or do not exhibit durable responses due to primary or adaptive/acquired immune resistance mechanisms of the tumor microenvironment. These suppressive programs are myriad, different between patients with ostensibly the same cancer type, and can harness multiple cell types to reinforce their stability. Consequently, the overall benefit of monotherapies remains limited. Cutting-edge technologies now allow for extensive tumor profiling, which can be used to define tumor cell intrinsic and extrinsic pathways of primary and/or acquired immune resistance, herein referred to as features or feature sets of immune resistance to current therapies. We propose that cancers can be characterized by immune resistance archetypes, comprised of five feature sets encompassing known immune resistance mechanisms. Archetypes of resistance may inform new therapeutic strategies that concurrently address multiple cell axes and/or suppressive mechanisms, and clinicians may consequently be able to prioritize targeted therapy combinations for individual patients to improve overall efficacy and outcomes.
AB - Anticancer immunotherapies, such as immune checkpoint inhibitors, bispecific antibodies, and chimeric antigen receptor T cells, have improved outcomes for patients with a variety of malignancies. However, most patients either do not initially respond or do not exhibit durable responses due to primary or adaptive/acquired immune resistance mechanisms of the tumor microenvironment. These suppressive programs are myriad, different between patients with ostensibly the same cancer type, and can harness multiple cell types to reinforce their stability. Consequently, the overall benefit of monotherapies remains limited. Cutting-edge technologies now allow for extensive tumor profiling, which can be used to define tumor cell intrinsic and extrinsic pathways of primary and/or acquired immune resistance, herein referred to as features or feature sets of immune resistance to current therapies. We propose that cancers can be characterized by immune resistance archetypes, comprised of five feature sets encompassing known immune resistance mechanisms. Archetypes of resistance may inform new therapeutic strategies that concurrently address multiple cell axes and/or suppressive mechanisms, and clinicians may consequently be able to prioritize targeted therapy combinations for individual patients to improve overall efficacy and outcomes.
KW - cytotoxicity, immunologic
KW - gene expression profiling
KW - immune evation
KW - review
KW - tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85164035868&partnerID=8YFLogxK
U2 - 10.1136/jitc-2022-006533
DO - 10.1136/jitc-2022-006533
M3 - Article
C2 - 37399356
AN - SCOPUS:85164035868
SN - 2051-1426
VL - 11
JO - Journal for ImmunoTherapy of Cancer
JF - Journal for ImmunoTherapy of Cancer
IS - 6
M1 - 006533
ER -