Cancer testis antigen burden (CTAB): a novel biomarker of tumor-associated antigens in lung cancer

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Cancer-testis antigens (CTAs) are aberrantly expressed in various cancers, including lung cancer, correlating with metastasis, progression, and poor prognosis.
• Accurate identification and quantification of CTAs are crucial for advancing lung cancer diagnosis, prognosis, and therapeutic strategies.
• This study introduces cancer testis antigen burden (CTAB) as a novel biomarker derived from CTA co-expression for predicting immunotherapy response.

Purpose of the Study:

• To investigate and quantify the co-expression of CTAs in lung cancer.
• To develop and validate CTAB as a novel biomarker for immunotherapy response in non-small cell lung cancer (NSCLC).
• To assess the correlation of CTAB with existing biomarkers like PD-L1 and tumor mutational burden (TMB) and its impact on patient survival and objective response rate (ORR).

Main Methods:

• Comprehensive genomic and immune profiling (CGIP) was performed on formalin-fixed paraffin-embedded (FFPE) tumor samples from discovery and retrospective NSCLC cohorts.
• Seventeen CTAs were quantified, and their expression was summed to derive the CTAB score.
• Kaplan-Meier survival analyses and Fisher's exact test were used to evaluate overall survival (OS) and ORR, respectively, in relation to CTAB levels and treatment groups.

Main Results:

• CTAs were found to be highly co-expressed in the discovery cohort (p < 0.05).
• CTAB showed no significant correlation with PD-L1 expression but a notable correlation with TMB (R = 0.11, p < 10^-13).
• High CTAB was associated with improved OS in NSCLC patients treated with pembrolizumab monotherapy (p = 0.027) and greater ORR compared to combination therapy (p = 0.02).

Conclusions:

• CTA co-expression can be reliably quantified using CGIP in solid tumors.
• CTAB serves as an independent biomarker from PD-L1, potentially reflecting unmeasured aspects of tumor immunogenicity.
• The improved survival and response rates in high CTAB NSCLC patients treated with pembrolizumab highlight a unique immune response mechanism warranting further investigation.