2171 - CCND1 Amplification Contributes to Immunosuppression in Head and Neck Squamous Cell Carcinoma and the Association with a Poor Response to Immune Checkpoint Inhibitors

Background

Copy number alterations in cyclin D1 (CCND1) relevant to malignant biological behavior exist in solid tumors, including head and neck squamous cell cancer (HNSCC). The prevalence and utility of CCND1 amplification as a biomarker for the clinical response to immune checkpoint inhibitors (ICIs) therapy is unknown.

Methods

This was a three-cohort pooled study, 6904 samples from 6540 patients from the Geneplus Insitute, 10562 samples from the TCGA and 10614 samples from the MSKCC were statistically analyzed. Next-generation sequencing assays were performed in tumor samples at the Geneplus Institute. Genomic, transcriptomic, and clinical data were obtained from TCGA and MSKCC. Comprehensive profiling was performed to determine the prevalence of CCND1 amplification and their correlation with the prognosis and the response to ICIs. Assessment of the CCND1 amplification frequency, overall survival (OS), gene set enrichment analysis (GSEA) and immune profile in solid tumors.

Results

In HNSCC, 7 cases (25.00%) were identified CCND1 amplification in the Chinese cohort, 120 cases (23.21%) in the TCGA cohort, and 5 cases (9.43%) in the MSKCC cohort. Survival analysis showed that CCND1 amplification was an independent prognostic factor for poor outcome in HNSCC as well as for pan-cancer in the TCGA and MSKCC populations. Furthermore, in the MSKCC cohort, patients receiving ICIs with CCND1 amplification had a shorter OS compared with neutral patients (HR, 1.63; 95%CI, 1.09–2.43; median OS, 11.0m vs. 18.0m; P = .0024), especial in the high-TMB subgroup (HR, 2.82; 95%CI, 1.11–7.20; median OS, 10.0m vs. 41.0m; P = .0003). Comparing the transcriptome between amplification and neutral groups in six solid tumors from the TCGA cohort showed various degrees of immunosuppression in the tumor microenvironment (TME), especially in HNSCC. The GSEA suggested that multiple aggressive, immunosuppressive and angiogenic hallmarks correlate with CCND1 amplification in HNSCC.

Conclusions

These findings indicate that CCND1 amplification may be a key point related to immunosuppression in TME and multiple malignancy hallmarks, and it hinders not only the natural host immune responses but also the efficacy of ICIs.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Chuan Ben Chen.

Funding

Ministry of Health P.R.China (Grant No. WKJ2016-2-33).

Disclosure

All authors have declared no conflicts of interest.