Leveraging immune resistance archetypes in solid cancer to inform next-generation anticancer therapies
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 01, 2023
- Source ID
- 10.1136/jitc-2022-006533
Entities
People
- Abigail E Overacre
- Aitziber Buqué
- Brendan Horton
- Bridget P Keenan
- David A Braun
- Fan Zhang
- Jennifer L Guerriero
- Kristin G Anderson
- Marco Ruella
- Omkara Veeranki
- Sarah B. Gitto
- Teresa S Kim
- Todd Triplett
- Vivek Verma
Organizations
- Cancer Prevention and Research Institute of Texas
- Cholangiocarcinoma Foundation
- Concern Foundation
- Congressionally Directed Medical Research Programs
- Damon Runyon Cancer Research Foundation
- Emerson Collective
- Fred Hutchinson Cancer Center
- Gabrielle’s Angel Foundation for Cancer Research
- Laffey-McHugh Foundation
- Leukemia & Lymphoma Society
- Lymphoma Research Foundation
- National Cancer Institute
- National Center for Advancing Translational Sciences
- Ovarian Cancer Research Alliance
- Pittsburgh Foundation
- Rivkin Center for Ovarian Cancer
- Society for Immunotherapy of Cancer
- Susan G. Komen for the Cure
- The Cancer Center at the University of Minnesota
- University of California, San Francisco
- University of Florida
- University of Pennsylvania