SIRPG expression positively associates with an inflamed tumor microenvironment and response to PD-1 blockade
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.High signal regulatory protein gamma (SIRPG) expression correlates with an inflamed tumor immune microenvironment and predicts better response to PD-1 blockade therapy in cancers like NSCLC and melanoma.
Area Of Science
- Immunology
- Oncology
- Genetics
Background
- Investigating the role of signal regulatory protein gamma (SIRPG) in cancer immunity.
- Understanding SIRPG's impact on tumor immune microenvironment (TME) phenotypes and T cell-mediated antitumor immunity.
- Assessing SIRPG's predictive value for response to programmed cell death protein 1 (PD-1) blockade therapy.
Purpose Of The Study
- To explore the association between SIRPG expression and TME phenotypes.
- To determine if SIRPG predicts response to PD-1 blockade in cancer patients.
- To elucidate the functional role of SIRPG in T cell immunity.
Main Methods
- Pan-cancer analysis of SIRPG expression and immune deconvolution using transcriptomic data.
- Analysis of transcriptomic and clinical data from 157 patients with non-small-cell lung cancer (NSCLC) and melanoma treated with PD-1 blockade.
- Single-cell RNA sequencing (scRNA-seq) to investigate SIRPG expression characteristics.
- In vitro experiments involving SIRPG knockdown or overexpression in Jurkat T cells.
Main Results
- High SIRPG expression linked to increased T cells, B cells, NK cells, M1 macrophages, and cytotoxic lymphocytes, alongside enhanced immune-modulatory factors.
- Conversely, high SIRPG correlated with lower neutrophils, M2 macrophages, and myeloid-derived suppressor cells.
- Favorable response to PD-1 blockade observed in NSCLC and melanoma patients with high SIRPG expression.
- scRNA-seq revealed SIRPG expression in CD8+ exhausted T and CD4+ regulatory T cells, positively associated with immune checkpoint expression (PDCD1, CTLA4).
- In vitro studies confirmed SIRPG facilitates PDCD1 and CTLA4 expression in T cells.
Conclusions
- High SIRPG expression signifies an inflamed immune phenotype in cancers.
- SIRPG serves as a promising predictive biomarker for PD-1 blockade therapy response.
- SIRPG represents a potential novel target for cancer immunotherapy.
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
Related Concept Videos
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...