Response to Immune Checkpoint Inhibitors Is Affected by Deregulations in the Antigen Presentation Machinery: A Systematic Review and Meta-Analysis
Research output: Contribution to journal › Review › Research › peer-review
Standard
Response to Immune Checkpoint Inhibitors Is Affected by Deregulations in the Antigen Presentation Machinery : A Systematic Review and Meta-Analysis. / Rasmussen, Maria; Durhuus, Jon Ambæk; Nilbert, Mef; Andersen, Ove; Therkildsen, Christina.
In: Journal of Clinical Medicine, Vol. 12, No. 1, 329, 2023.Research output: Contribution to journal › Review › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Response to Immune Checkpoint Inhibitors Is Affected by Deregulations in the Antigen Presentation Machinery
T2 - A Systematic Review and Meta-Analysis
AU - Rasmussen, Maria
AU - Durhuus, Jon Ambæk
AU - Nilbert, Mef
AU - Andersen, Ove
AU - Therkildsen, Christina
N1 - Publisher Copyright: © 2022 by the authors.
PY - 2023
Y1 - 2023
N2 - Immune checkpoint inhibitors (ICI) targeting programmed death 1 (PD-1), its ligand (PD-L1), or cytotoxic T-lymphocyte antigen 4 (CTLA-4) have shown promising results against multiple cancers, where they reactivate exhausted T cells primed to eliminate tumor cells. ICI therapies have been particularly successful in hypermutated cancers infiltrated with lymphocytes. However, resistance may appear in tumors evading the immune system through alternative mechanisms than the PD-1/PD-L1 or CTLA-4 pathways. A systematic pan-cancer literature search was conducted to examine the association between alternative immune evasion mechanisms via the antigen presentation machinery (APM) and resistance towards ICI treatments targeting PD-1 (pembrolizumab and nivolumab), PD-L1 (durvalumab, avelumab, and atezolizumab), and CTLA-4 (ipilimumab). The APM proteins included the human leucocyte antigen (HLA) class I, its subunit beta-2 microglobulin (B2M), the transporter associated with antigen processing (TAP) 1, TAP2, and the NOD-like receptor family CARD domain containing 5 (NLRC5). In total, 18 cohort studies (including 21 original study cohorts) containing 966 eligible patients and 9 case studies including 12 patients were reviewed. Defects in the APM significantly predicted poor clinical benefit with an odds ratio (OR) of 0.39 (95% CI 0.24–0.63, p < 0.001). The effect was non-significant, when considering complete and partial responses only (OR = 0.52, 95% CI 0.18–1.47, p = 0.216). In summary, the APM contains important targets for tumorigenic alterations which may explain insensitivity towards ICI therapy.
AB - Immune checkpoint inhibitors (ICI) targeting programmed death 1 (PD-1), its ligand (PD-L1), or cytotoxic T-lymphocyte antigen 4 (CTLA-4) have shown promising results against multiple cancers, where they reactivate exhausted T cells primed to eliminate tumor cells. ICI therapies have been particularly successful in hypermutated cancers infiltrated with lymphocytes. However, resistance may appear in tumors evading the immune system through alternative mechanisms than the PD-1/PD-L1 or CTLA-4 pathways. A systematic pan-cancer literature search was conducted to examine the association between alternative immune evasion mechanisms via the antigen presentation machinery (APM) and resistance towards ICI treatments targeting PD-1 (pembrolizumab and nivolumab), PD-L1 (durvalumab, avelumab, and atezolizumab), and CTLA-4 (ipilimumab). The APM proteins included the human leucocyte antigen (HLA) class I, its subunit beta-2 microglobulin (B2M), the transporter associated with antigen processing (TAP) 1, TAP2, and the NOD-like receptor family CARD domain containing 5 (NLRC5). In total, 18 cohort studies (including 21 original study cohorts) containing 966 eligible patients and 9 case studies including 12 patients were reviewed. Defects in the APM significantly predicted poor clinical benefit with an odds ratio (OR) of 0.39 (95% CI 0.24–0.63, p < 0.001). The effect was non-significant, when considering complete and partial responses only (OR = 0.52, 95% CI 0.18–1.47, p = 0.216). In summary, the APM contains important targets for tumorigenic alterations which may explain insensitivity towards ICI therapy.
KW - antigen presenting machinery
KW - biomarkers
KW - immunoediting
KW - immunotherapy
KW - melanoma
KW - non-small cell lung cancer
U2 - 10.3390/jcm12010329
DO - 10.3390/jcm12010329
M3 - Review
C2 - 36615128
AN - SCOPUS:85145824757
VL - 12
JO - Journal of Clinical Medicine
JF - Journal of Clinical Medicine
SN - 2077-0383
IS - 1
M1 - 329
ER -
ID: 333481210