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Damrauer JS, Roell KR, Smith MA, et al. Identification of a Novel Inflamed Tumor Microenvironment Signature as a Predictive Biomarker of Bacillus Calmette-Guérin Immunotherapy in Non-Muscle-Invasive Bladder Cancer. Clin Cancer Res. 2021;27(16):4599-4609doi: 10.1158/1078-0432.CCR-21-0205.
Damrauer, J. S., Roell, K. R., Smith, M. A., Sun, X., Kirk, E. L., Hoadley, K. A., Benefield, H. C., Iyer, G., Solit, D. B., Milowsky, M. I., Kim, W. Y., Nielsen, M. E., Wobker, S. E., Dalbagni, G., Al-Ahmadie, H. A., Olshan, A. F., Bochner, B. H., Furberg, H., Troester, M. A., & Pietzak, E. J. (2021). Identification of a Novel Inflamed Tumor Microenvironment Signature as a Predictive Biomarker of Bacillus Calmette-Guérin Immunotherapy in Non-Muscle-Invasive Bladder Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research, 27(16), 4599-4609. https://doi.org/10.1158/1078-0432.CCR-21-0205
Damrauer, Jeffrey S, et al. "Identification of a Novel Inflamed Tumor Microenvironment Signature as a Predictive Biomarker of Bacillus Calmette-Guérin Immunotherapy in Non-Muscle-Invasive Bladder Cancer." Clinical cancer research : an official journal of the American Association for Cancer Research vol. 27,16 (2021): 4599-4609. doi: https://doi.org/10.1158/1078-0432.CCR-21-0205
Damrauer JS, Roell KR, Smith MA, Sun X, Kirk EL, Hoadley KA, Benefield HC, Iyer G, Solit DB, Milowsky MI, Kim WY, Nielsen ME, Wobker SE, Dalbagni G, Al-Ahmadie HA, Olshan AF, Bochner BH, Furberg H, Troester MA, Pietzak EJ. Identification of a Novel Inflamed Tumor Microenvironment Signature as a Predictive Biomarker of Bacillus Calmette-Guérin Immunotherapy in Non-Muscle-Invasive Bladder Cancer. Clin Cancer Res. 2021 Aug 15;27(16):4599-4609. doi: 10.1158/1078-0432.CCR-21-0205. Epub 2021 Jun 11. PMID: 34117034; PMCID: PMC8416390.
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Clin Cancer Res. 2021 Aug 15;27(16):4599-4609. doi: 10.1158/1078-0432.CCR-21-0205. Epub 2021 Jun 11.

Identification of a Novel Inflamed Tumor Microenvironment Signature as a Predictive Biomarker of Bacillus Calmette-Guérin Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Clinical cancer research : an official journal of the American Association for Cancer Research

Jeffrey S Damrauer, Kyle R Roell, Markia A Smith, Xuezheng Sun, Erin L Kirk, Katherine A Hoadley, Halei C Benefield, Gopakumar Iyer, David B Solit, Matthew I Milowsky, William Y Kim, Matthew E Nielsen, Sara E Wobker, Guido Dalbagni, Hikmat A Al-Ahmadie, Andrew F Olshan, Bernard H Bochner, Helena Furberg, Melissa A Troester, Eugene J Pietzak

Affiliations

  1. University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina.
  2. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
  3. Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
  4. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
  5. Department of Medicine (Genitourinary Oncology Service), Memorial Sloan Kettering Cancer Center, New York, New York.
  6. Department of Medicine, Weill Cornell Medicine, New York, New York.
  7. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
  8. Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
  9. Department of Urology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
  10. Department of Surgery (Urology Service), Memorial Sloan Kettering Cancer Center, New York, New York.
  11. Department of Urology, Weill Cornell Medicine, New York, New York.
  12. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
  13. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
  14. Department of Surgery (Urology Service), Memorial Sloan Kettering Cancer Center, New York, New York. [email protected].

PMID: 34117034 PMCID: PMC8416390 DOI: 10.1158/1078-0432.CCR-21-0205

Abstract

PURPOSE: Improved risk stratification and predictive biomarkers of treatment response are needed for non-muscle-invasive bladder cancer (NMIBC). Here we assessed the clinical utility of targeted RNA and DNA molecular profiling in NMIBC.

EXPERIMENTAL DESIGN: Gene expression in NMIBC samples was profiled by NanoString nCounter, an RNA quantification platform, from two independent cohorts (

RESULTS: Molecular subtypes distinguished between low-grade Ta tumors with FGFR3 mutations and overexpression (UROMOL-class 1) and tumors with more aggressive clinicopathologic characteristics (UROMOL-classes 2 and 3), which were significantly enriched with TERT promoter mutations. However, UROMOL subclasses were not associated with recurrence after bacillus Calmette-Guérin (BCG) immunotherapy in two independent cohorts. In contrast, a novel expression signature of an inflamed tumor microenvironment (TME) was associated with improved recurrence-free survival after BCG. Expression of immune checkpoint genes (PD-L1/PD-1/CTLA-4) was associated with an inflamed TME, but not with higher recurrence rates after BCG. FGFR3 mutations and overexpression were both associated with low immune signatures.

CONCLUSIONS: Assessment of the immune TME, rather than molecular subtypes, is a promising predictive biomarker of BCG response. Modulating the TME in an immunologically "cold" tumor warrants further investigation. Integrated transcriptomic and exome sequencing should improve treatment selection in NMIBC.

©2021 The Authors; Published by the American Association for Cancer Research.

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