Circulating tumor cell subtypes and T-cell populations as prognostic biomarkers to combination immunotherapy in patients with metastatic genitourinary cancer

Heather J. Chalfin, Tiziano Pramparo, Amir Mortazavi, Scot A. Niglio, Joseph D. Schonhoft, Adam Jendrisak, Yen Lin Chu, Robin Richardson, Rachel Krupa, Amanda K.L. Anderson, Yipeng Wang, Ryan Dittamore, Sumanta K. Pal, Primo N. Lara, Mark N. Stein, David I. Quinn, Seth M. Steinberg, Lisa M. Cordes, Lisa Ley, Marissa MallekOlena Sierra Ortiz, Rene Costello, Jacqueline Cadena, Carlos Diaz, James L. Gulley, William L. Dahut, Howard Streicher, John J. Wright, Jane B. Trepel, Donald P. Bottaro, Andrea B. Apolo

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Circulating tumor cells (CTC) are under investigation as a minimally invasive liquid biopsy that may improve risk stratification and treatment selection. CTCs uniquely allow for digital pathology of individual malignant cell morphology and marker expression. We compared CTC features and T-cell counts with survival endpoints in a cohort of patients with metastatic genitourinary cancer treated with combination immunotherapy. Experimental Design: Markers evaluated included pan-CK/ CD45/PD-L1/DAPI for CTCs and CD4/CD8/Ki-67/DAPI for T cells. ANOVA was used to compare CTC burden and T-cell populations across timepoints. Differences in survival and disease progression were evaluated using the maximum log-rank test. Results: From December 2016 to January 2019, 183 samples from 81 patients were tested. CTCs were found in 75% of patients at baseline. CTC burden was associated with shorter overall survival (OS) at baseline (P ¼ 0.022), but not on-therapy. Five morphologic subtypes were detected, and the presence of two specific subtypes with unique cellular features at baseline and on-therapy was associated with worse OS (0.9-2.3 vs. 28.2 months; P < 0.0001-0.013). Increasing CTC heterogeneity on-therapy had a trend toward worse OS (P ¼ 0.045). PD-L1þ CTCs on-therapy were associated with worse OS (P < 0.01, cycle 2). Low baseline and on-therapy CD4/CD8 counts were also associated with poor OS and response category. Conclusions: Shorter survival may be associated with high CTC counts at baseline, presence of specific CTC morphologic subtypes, PD-L1þ CTCs, and low %CD4/8 T cells in patients with metastatic genitourinary cancer. A future study is warranted to validate the prognostic utility of CTC heterogeneity and detection of specific CTC morphologies.

Original languageEnglish (US)
Pages (from-to)1391-1398
Number of pages8
JournalClinical Cancer Research
Volume27
Issue number5
DOIs
StatePublished - Mar 1 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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