KEY TAKEAWAYS
- The UPTIDER trial studied the expression levels of immune checkpoint markers in hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer.
- Using bulk RNA sequencing, researchers analyzed samples from 10 UPTIDER primary HR+/HER2- BC pts.
- The research highlighted the expression of IC markers in M from HR+/HER2- primary BC pts and the impact of ER expression and histology.
This study analyzed the expression levels of immune checkpoint (IC) markers in multiple metastases (M) and primary tumors (P) from primary hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) patients (pts) who participated in the postmortem tissue donation program, UPTIDER.
Researchers analyzed 326 samples (23 untreated P and 290 postmortem M samples) from 10 UPTIDER primary HR+/HER2- BC pts using bulk RNA sequencing (Lexogen). A quality control (QC) was set up, and gene counts were adjusted through variance stabilizing transformation for the assigned reads, totaling 500000. We focused on clinically-investigated IC markers in BC, such as BTLA, CD40, CD47, CD86, CD137, CD137L, CD158A, CD226, CTLA4, ICOS, LAG3, OX40, PD-1, PD-L1, TIM3, and TIGIT from literature and clinicaltrials.gov. The study assessed histology (invasive lobular, ILC, and breast cancer of no special type, NST) and ER status in the matched FFPE samples. Researchers utilized logistic linear regressions with data clustering by patient to evaluate the associations between sample status (outcome: M vs P/ ER+ vs ER- for M) and individual gene expression (using the generalized estimating equation method). The study also determined the association between sample-specific postmortem interval (ssPMI) and gene expression by repeatedly sampling (at 1.5h intervals) of the same M in 7 pts.
Of the 326 samples examined, 324 passed quality control (289 M and 22 P), and the IC expression was stable with increasing ssPMI. M showed higher expression of TIM3 and BTLA, and lower expression of PD-1, PD-L1, CTLA4, LAG3, OX40, and TIGIT, compared to P, with an odds ratio range of 0.27-0.53 and p<0.05. Intra-patient inter-M heterogeneity was observed across all markers. BTLA, CD86, CTLA4, OX40, and TIM3 had greater expression in NST M than ILC M, with an odds ratio of 1-1.43. PD-L1, CD47, LAG3, CD40, and TIGIT showed higher expression in ER+ compared to ER- M in both NST and ILC, with an odds ratio range of 1.02-1.37 for NST and 1.12-5.52 for ILC. PD-1 exhibited the most negligible expression in M, while TIM3 was highly expressed.
The research provides insights into the expression of IC markers in M from HR+/HER2- primary BC pts. It also examined the impact of ER expression and histology.
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04531696
Pabba, A., Zels, G., De Schepper, M., Geukens, T., Baelen, K.V., Maetens, M., Nguyen, H.L., Mahdami, A., Boeckx, B., Vanderheyden, E., Punie, K., Neven, P., Wildiers, H., Bogaert, W.V.D., Biganzoli, E., Lambrechts, D., Floris, G., Richard, F., Desmedt, C. Annals of Oncology (2023) 8 (1suppl_4): 101218-101218. 10.1016/esmoop/esmoop101218.
