Dataset Information

CDKN2A Alterations and Response to Immunotherapy in Solid Tumors.

ABSTRACT:

Purpose

Immune checkpoint inhibitors (ICI) have shown clinical benefit in many types of metastatic cancers with only a few predictive biomarkers identified so far. CDKN2A is commonly altered in human cancers, but prior studies have provided conflicting evidence regarding the association between CDKN2A genomic alterations (GA) and response to ICIs. Herein, we examined the impact of loss-of-function CDKN2A alterations on response and survival in patients treated with ICIs.

Experimental design

We studied the association between loss-of-function CDKN2A alterations and the response to ICIs in two independent cohorts of six different cancer types. Seven hundred and eighty-nine patients treated at Dana-Farber Cancer Institute (DFCI; Boston, MA) and 1,250 patients treated at Memorial Sloan Kettering Cancer Center (MSKCC; New York, NY) were included in the final analysis. Patients' tumors were sequenced using Oncopanel or MSK-IMPACT. RNA sequencing data from The Cancer Genome Atlas and IMvigor210 were used to investigate differences in the tumor microenvironment.

Results

In the DFCI cohort, CDKN2A GAs were associated with poor response and survival in patients with urothelial carcinoma treated with ICIs, but not those treated with platinum-based therapy. Similarly, CDKN2A GAs were associated with worse outcomes in the MSKCC urothelial carcinoma cohort treated with ICIs. There was no association of CDKN2A status with ICI treatment outcome in five other cancers: esophagogastric, head and neck, non-small cell lung, renal cell carcinoma, and melanoma. Immuno-inflammatory pathways were significantly reduced in expression in CDKN2A-altered tumors.

Conclusions

Our data show that CDKN2A GAs were associated with reduced benefit from ICI therapy in urothelial carcinoma as well as changes in the tumor-immune microenvironment.

SUBMITTER: Adib E

PROVIDER: S-EPMC8900067 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Publications

<i>CDKN2A</i> Alterations and Response to Immunotherapy in Solid Tumors.

Adib Elio E Nassar Amin H AH Akl Elie W EW Abou Alaiwi Sarah S Nuzzo Pier Vitale PV Mouhieddine Tarek H TH Sonpavde Guru G Haddad Robert I RI Mouw Kent W KW Giannakis Marios M Hodi F Stephen FS Shukla Sachet A SA Gusev Alexander A Braun David A DA Choueiri Toni K TK Kwiatkowski David J DJ

Clinical cancer research : an official journal of the American Association for Cancer Research 20210601 14

<h4>Purpose</h4>Immune checkpoint inhibitors (ICI) have shown clinical benefit in many types of metastatic cancers with only a few predictive biomarkers identified so far. <i>CDKN2A</i> is commonly altered in human cancers, but prior studies have provided conflicting evidence regarding the association between <i>CDKN2A</i> genomic alterations (GA) and response to ICIs. Herein, we examined the impact of loss-of-function <i>CDKN2A</i> alterations on response and survival in patients treated with I ...[more]

PMID: 34074656

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