TY - JOUR
T1 - MHC Class I Downregulation in Cancer
T2 - Underlying Mechanisms and Potential Targets for Cancer Immunotherapy
AU - Cornel, Annelisa M
AU - Mimpen, Iris L
AU - Nierkens, Stefan
N1 - Funding Information:
Funding: This research was funded by Villa Joep Foundation, Grant number IWOV-Actief.51381.180034.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/7/2
Y1 - 2020/7/2
N2 - In recent years, major advances have been made in cancer immunotherapy. This has led to significant improvement in prognosis of cancer patients, especially in the hematological setting. Nonetheless, translation of these successes to solid tumors was found difficult. One major mechanism through which solid tumors can avoid anti-tumor immunity is the downregulation of major histocompatibility complex class I (MHC-I), which causes reduced recognition by- and cytotoxicity of CD8+ T-cells. Downregulation of MHC-I has been described in 40-90% of human tumors, often correlating with worse prognosis. Epigenetic and (post-)transcriptional dysregulations relevant in the stabilization of NFkB, IRFs, and NLRC5 are often responsible for MHC-I downregulation in cancer. The intrinsic reversible nature of these dysregulations provides an opportunity to restore MHC-I expression and facilitate adaptive anti-tumor immunity. In this review, we provide an overview of the mechanisms underlying reversible MHC-I downregulation and describe potential strategies to counteract this reduction in MHC-I antigen presentation in cancer.
AB - In recent years, major advances have been made in cancer immunotherapy. This has led to significant improvement in prognosis of cancer patients, especially in the hematological setting. Nonetheless, translation of these successes to solid tumors was found difficult. One major mechanism through which solid tumors can avoid anti-tumor immunity is the downregulation of major histocompatibility complex class I (MHC-I), which causes reduced recognition by- and cytotoxicity of CD8+ T-cells. Downregulation of MHC-I has been described in 40-90% of human tumors, often correlating with worse prognosis. Epigenetic and (post-)transcriptional dysregulations relevant in the stabilization of NFkB, IRFs, and NLRC5 are often responsible for MHC-I downregulation in cancer. The intrinsic reversible nature of these dysregulations provides an opportunity to restore MHC-I expression and facilitate adaptive anti-tumor immunity. In this review, we provide an overview of the mechanisms underlying reversible MHC-I downregulation and describe potential strategies to counteract this reduction in MHC-I antigen presentation in cancer.
KW - Adaptive immune involvement
KW - Antigen presentation
KW - Cancer immunotherapy
KW - MHC-I downregulation
KW - Tumor immunogenicity
UR - http://www.scopus.com/inward/record.url?scp=85087406222&partnerID=8YFLogxK
U2 - 10.3390/cancers12071760
DO - 10.3390/cancers12071760
M3 - Review article
C2 - 32630675
SN - 2072-6694
VL - 12
SP - 1
EP - 33
JO - Cancers
JF - Cancers
IS - 7
M1 - 1760
ER -