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ePoster Display

1288P - Mutations in MTOR pathway and response of immune checkpoint inhibitors

Date

16 Sep 2021

Session

ePoster Display

Topics

Translational Research;  Immunotherapy

Tumour Site

Presenters

Lei Cheng

Citation

Annals of Oncology (2021) 32 (suppl_5): S949-S1039. 10.1016/annonc/annonc729

Authors

L. Cheng, B. Han

Author affiliations

  • Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, 200030 - Shanghai/CN

Resources

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Abstract 1288P

Background

MTOR pathway plays central role in metabolisms and cell cycle modulation, modulating cell proliferation and metastasis in cancers. However, whether it is associated with cancer immune checkpoint therapy is unclear.

Methods

We extracted mutations in 23 genes in MTOR pathway from a MSKCC cohort of 1661 cancer patients, and fitted an optimal survival model by setpwise Cox regression analysis. The 8 genes filtered for the optimal Cox model were used for combine analysis for predicting survival of 1661 MSKCC cancer patients received immune checkpoint inhibitors (ICI) and results were validated in other 288 patients from 5 ICI-treated cohorts. Further TCGA pancancer bioinformatics analysis were adopted to determine the immunity of the mutation tumors (immunologically ‘cold’ or ‘hot’ tumors) in comparison with the wild tumors.

Results

Stepwise Cox regression identified mutations in 8 genes, including MTOR, FGFR2, PIK3C3, FGFR4, FGFR1, FGF3, AKT1 and RPTOR, that were fitted a optimal Cox model in predicting survival of 1661 cancer patients received ICI from MSKCC cohort. Combined analysis found that the 8 MTOR genes mutations were associated with better survival of the ICI treated patients (HR=0.76, P=0.034), which was validated in other 288 patients from independent 5 cohorts. This association seemed significant in patients not only with high tumor mutation burden (TMB) but those with low TMB (P<0.05 for all). Further analysis using TCGA pancancer dataset revealed higher antigen presenting machinery score, CD8+ T cells and M1 macrophages infiltration, but lower M2 macrophages in the comparison of mutation versus wild patients. The mutation patients were enriched in immune checkpoint genes and pro-immune chemokines genes expression.

Conclusions

These results suggest MTOR pathway mutations make the tumor immunologically ‘hot’ and are associated with better response of cancer immune checkpoint inhibitors.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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