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Transcriptomic Correlates of Immunologic Activation in Head and Neck and Cervical Cancer
Cristina Saiz-Ladera1, Mariona Baliu-Piqué1, Francisco J Cimas2
1Experimental Therapeutics Unit, Medical Oncology Department, Hospital Clínico Universitario San Carlos (HCSC), Instituto de Investigación Sanitaria (IdISSC), Madrid, Spain.
Abstract:
Targeting the immune system has emerged as an effective therapeutic strategy for the treatment of various tumor types, including Head and Neck Squamous Cell Carcinoma (HNSCC) and Non-small-Cell Lung Cancer (NSCLC), and checkpoint inhibitors have shown to improve patient survival in these tumor types. Unfortunately, not all cancers respond to these agents, making it necessary to identify responsive tumors. Several biomarkers of response have been described and clinically tested. As of yet what seems to be clear is that a pre-activation state of the immune system is necessary for these agents to be efficient. In this study, using established transcriptomic signatures, we identified a group of gene combination associated with favorable outcome in HNSCC linked to a higher presence of immune effector cells. CD2, CD3D, CD3E, and CXCR6 combined gene expression is associated with improved outcome of HNSCC patients and an increase of infiltrating immune effector cells. This new signature also identifies a subset of cervical squamous cell carcinoma (CSCC) patients with favorable prognosis, who show an increased presence of immune effector cells in the tumor, which outcome shows similarities with the HP-positive HNSCC cohort of patients. In addition, CD2, CD3D, CD3E, and CXCR6 signature is able to predict the best favorable prognosis in terms of overall survival of CSSC patients. Of note, these findings were not reproduced in other squamous cell carcinomas like esophageal SCC or lung SCC. Prospective confirmatory studies should be employed to validate these findings.
Insights
A new gene signature including CD2, CD3D, CD3E, and CXCR6 predicts better outcomes in Head and Neck Squamous Cell Carcinoma (HNSCC) and cervical squamous cell carcinoma (CSCC) by indicating a stronger immune response. This finding may help identify patients likely to benefit from immunotherapy.
Area of Science:
- Immunogenomics
- Cancer Biomarkers
- Translational Oncology
Background:
- Immunotherapy, particularly checkpoint inhibitors, has improved survival in Head and Neck Squamous Cell Carcinoma (HNSCC) and Non-small-Cell Lung Cancer (NSCLC).
- Identifying responsive tumors is crucial as not all patients benefit from these treatments, necessitating robust biomarkers.
- A pre-activated immune system is essential for the efficacy of immune checkpoint inhibitors.
Purpose of the Study:
- To identify novel gene signatures associated with favorable outcomes in HNSCC.
- To investigate the relationship between specific gene expression patterns and the presence of immune effector cells.
- To evaluate the predictive potential of identified signatures in other squamous cell carcinoma subtypes.
Main Methods:
- Utilized established transcriptomic signatures to analyze gene expression data.
- Focused on combinations of genes, specifically CD2, CD3D, CD3E, and CXCR6, in relation to patient outcomes.
- Correlated gene expression with the presence of infiltrating immune effector cells in tumor tissues.
Main Results:
- A combined gene expression signature of CD2, CD3D, CD3E, and CXCR6 was associated with improved outcomes in HNSCC patients.
- This signature correlated with a higher infiltration of immune effector cells in HNSCC tumors.
- The signature also identified a subset of cervical squamous cell carcinoma (CSCC) patients with favorable prognosis and increased immune cell infiltration, showing similar outcomes to HPV-positive HNSCC.
Conclusions:
- The CD2, CD3D, CD3E, and CXCR6 gene signature serves as a potential biomarker for predicting favorable prognosis and increased immune cell presence in HNSCC and CSCC.
- This signature accurately predicts overall survival in CSCC patients.
- The findings were specific to HNSCC and CSCC, not being replicated in esophageal or lung squamous cell carcinomas, highlighting tissue-specific biomarker potential.
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