TY - JOUR
T1 - Chromatin Remodelers Are Regulators of the Tumor Immune Microenvironment
AU - Chaudhri, Apoorvi
AU - Lizee, Gregory
AU - Hwu, Patrick
AU - Rai, Kunal
N1 - Publisher Copyright:
© 2024 American Association for Cancer Research.
PY - 2024/4/1
Y1 - 2024/4/1
N2 - Immune checkpoint inhibitors show remarkable responses in a wide range of cancers, yet patients develop adaptive resistance. This necessitates the identification of alternate therapies that synergize with immunotherapies. Epigenetic modifiers are potent mediators of tumor-intrinsic mechanisms and have been shown to regulate immune response genes, making them prime targets for therapeutic combinations with immune checkpoint inhibitors. Some success has been observed in early clinical studies that combined immunotherapy with agents targeting DNA methylation and histone modification; however, less is known about chromatin remodeler-targeted therapies. Here, we provide a discussion on the regulation of tumor immunogenicity by the chromatin remodeling SWI/SNF complex through multiple mechanisms associated with immunotherapy response that broadly include IFN signaling, DNA damage, mismatch repair, regulation of oncogenic programs, and polycomb-repressive complex antagonism. Context-dependent targeting of SWI/SNF subunits can elicit opportunities for synthetic lethality and reduce T-cell exhaustion. In summary, alongside the significance of SWI/SNF subunits in predicting immunotherapy outcomes, their ability to modulate the tumor immune landscape offers opportunities for therapeutic intervention.
AB - Immune checkpoint inhibitors show remarkable responses in a wide range of cancers, yet patients develop adaptive resistance. This necessitates the identification of alternate therapies that synergize with immunotherapies. Epigenetic modifiers are potent mediators of tumor-intrinsic mechanisms and have been shown to regulate immune response genes, making them prime targets for therapeutic combinations with immune checkpoint inhibitors. Some success has been observed in early clinical studies that combined immunotherapy with agents targeting DNA methylation and histone modification; however, less is known about chromatin remodeler-targeted therapies. Here, we provide a discussion on the regulation of tumor immunogenicity by the chromatin remodeling SWI/SNF complex through multiple mechanisms associated with immunotherapy response that broadly include IFN signaling, DNA damage, mismatch repair, regulation of oncogenic programs, and polycomb-repressive complex antagonism. Context-dependent targeting of SWI/SNF subunits can elicit opportunities for synthetic lethality and reduce T-cell exhaustion. In summary, alongside the significance of SWI/SNF subunits in predicting immunotherapy outcomes, their ability to modulate the tumor immune landscape offers opportunities for therapeutic intervention.
UR - http://www.scopus.com/inward/record.url?scp=85189537259&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85189537259&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-23-2244
DO - 10.1158/0008-5472.CAN-23-2244
M3 - Review article
C2 - 38266066
AN - SCOPUS:85189537259
SN - 0008-5472
VL - 84
SP - 965
EP - 976
JO - Cancer Research
JF - Cancer Research
IS - 7
ER -