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Gregory J. Riely, MD, PhD


Researchers Develop Novel Pan-Cancer Biomarker to Assess Tumor Microenvironment

By: Amy MacDonald, MS
Posted: Friday, March 29, 2024

Cancer testis antigens (CTAs) are a family of at least 17 distinct proteins expressed exclusively in healthy placenta and testes tissue. However, CTAs have been found to aberrantly occur and actively promote tumorigenesis in numerous solid tumors (including lung cancer). Because of their differential expression, CTAs represent potential targets for immunotherapy.

Kyle C. Strickland, MD, of Duke University Medical Center, Durham, North Carolina, and colleagues used RNA sequencing to assess the distribution of CTA expression and co-expression across 22 types of solid tumors, including lung, breast, and colon. To facilitate the evaluation of so many distinct CTAs across these tumor types, they created a novel biomarker of aggregate CTA expression called “cancer testis antigen burden” (CTAB).

“We demonstrate that CTAB measures aspects of the tumor microenvironment not assessed by traditional biomarkers of immunotherapy response, namely PD-L1 expression and tumor mutational burden,” the researchers stated in the Journal of Translational Medicine. They suggested that use of CTAB may offer additional data about the susceptibility of many individual tumors to immunotherapy.

The researchers evaluated the prevalence of 17 CTA proteins from 5,624 patients with various types of untreated solid tumors (discovery cohort.) They compared these patients’ immunologic CTA signatures with those from 250 tumors taken from patients with non–small cell lung cancer (NSCLC; retrospective cohort) who had received the anti–PD-1 antibody pembrolizumab (with or without chemotherapy). They discovered the measured CTAs were highly co‐expressed (P < .05) in the discovery cohort, yet there was no apparent correlation between CTAB and PD‐L1 expression (r = 0.011, P = .45). Kaplan-Meier survival analysis of the immunotherapy‐treated NSCLC cohort revealed better overall survival with pembrolizumab (monotherapy)-treated patients who also exhibited a high CTAB (P = .027).

According to the researchers, CTA co‐expression may be reliably measured using the comprehensive genomic profiling described in their study. Furthermore, CTAB may prove to have particular utility as a biomarker in NSCLC.

Disclosure: For full disclosures of the study authors, visit

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