SIRPG expression positively associates with an inflamed tumor microenvironment and response to PD-1 blockade.
Cancer Immunol Immunother
; 73(8): 147, 2024 Jun 04.
Article
in En
| MEDLINE
| ID: mdl-38833156
ABSTRACT
BACKGROUND:
This study aimed to investigate the relationship between signal regulatory protein gamma (SIRPG) and tumor immune microenvironment phenotypes or T cell mediated-adaptive antitumor immunity, and its predictive value for response to PD-1 blockade in cancers.METHODS:
Pan-cancer analysis of SIRPG expression and immune deconvolution was performed using transcriptomic data across 33 tumor types. Transcriptomic and clinical data from 157 patients with non-small-cell lung cancer (NSCLC) and melanoma received PD-1 blockade were analyzed. Expression characteristics of SIRPG were investigated using single-cell RNA sequencing (scRNA-seq) data of 103,599 cells. The effect of SIRPG expression was evaluated via SIRPG knockdown or overexpression in Jurkat T cells.RESULTS:
The results showed that most cancers with high SIRPG expression had significantly higher abundance of T cells, B cells, NK cells, M1 macrophages and cytotoxic lymphocytes and increased expression level of immunomodulatory factors regulating immune cell recruitment, antigen presentation, T cell activation and cytotoxicity, but markedly lower abundance of neutrophils, M2 macrophages, and myeloid-derived suppressor cells. High SIRPG expression was associated with favorable response to PD-1 blockade in both NSCLC and melanoma. scRNA-seq data suggested SIRPG was mainly expressed in CD8+ exhausted T and CD4+ regulatory T cells, and positively associated with immune checkpoint expression including PDCD1 and CTLA4. In vitro test showed SIRPG expression in T cells could facilitate expression of PDCD1 and CTLA4.CONCLUSION:
High SIRPG expression is associated with an inflamed immune phenotype in cancers and favorable response to PD-1 blockade, suggesting it would be a promising predictive biomarker for PD-1 blockade and novel immunotherapeutic target.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tumor Microenvironment
/
Programmed Cell Death 1 Receptor
/
Immune Checkpoint Inhibitors
Limits:
Humans
Language:
En
Journal:
Cancer Immunol Immunother
/
Cancer immunol. immunother
/
Cancer immunology and immunotherapy
Journal subject:
ALERGIA E IMUNOLOGIA
/
NEOPLASIAS
/
TERAPEUTICA
Year:
2024
Type:
Article
Affiliation country:
China