Combinatorial biomarker for predicting outcomes to anti-PD-1 therapy in patients with metastatic clear cell renal cell carcinoma

Julie Stein Deutsch; Evan J Lipson; Ludmila Danilova; Suzanne L Topalian; Jaroslaw Jedrych; Ezra Baraban; Yasser Ged; Nirmish Singla; Toni K Choueiri; Saurabh Gupta; Robert J Motzer; David McDermott; Sabina Signoretti; Michael Atkins; Janis M Taube

doi:10.1016/j.xcrm.2023.100947

Combinatorial biomarker for predicting outcomes to anti-PD-1 therapy in patients with metastatic clear cell renal cell carcinoma

Cell Rep Med. 2023 Feb 21;4(2):100947. doi: 10.1016/j.xcrm.2023.100947.

Authors

Affiliations

¹ Department of Pathology, Johns Hopkins University, Baltimore, MD 21287, USA.
² Department of Oncology, Johns Hopkins University, Baltimore, MD 21287, USA; The Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD 21287, USA.
³ Department of Surgery, Johns Hopkins University, Baltimore, MD, USA; The Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD 21287, USA.
⁴ Department of Pathology, Johns Hopkins University, Baltimore, MD 21287, USA; Department of Dermatology, Johns Hopkins University, Baltimore, MD 21287, USA.
⁵ Department of Oncology, Johns Hopkins University, Baltimore, MD 21287, USA.
⁶ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁷ Bristol-Myers Squibb, Princeton, NJ, USA.
⁸ Department of Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁹ Department of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
¹⁰ Department of Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
¹¹ Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA.
¹² Department of Pathology, Johns Hopkins University, Baltimore, MD 21287, USA; Department of Oncology, Johns Hopkins University, Baltimore, MD 21287, USA; Department of Dermatology, Johns Hopkins University, Baltimore, MD 21287, USA; The Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD 21287, USA. Electronic address: [email protected].

Abstract

With a rapidly developing immunotherapeutic landscape for patients with metastatic clear cell renal cell carcinoma, biomarkers of efficacy are highly desirable to guide treatment strategy. Hematoxylin and eosin (H&E)-stained slides are inexpensive and widely available in pathology laboratories, including in resource-poor settings. Here, H&E scoring of tumor-infiltrating immune cells (TIL^plus) in pre-treatment tumor specimens using light microscopy is associated with improved overall survival (OS) in three independent cohorts of patients receiving immune checkpoint blockade. Necrosis score alone does not associate with OS; however, necrosis modifies the predictive effect of TIL^plus, a finding that has broad translational relevance for tissue-based biomarker development. PBRM1 mutational status is combined with H&E scores to further refine outcome predictions (OS, p = 0.007, and objective response, p = 0.04). These findings bring H&E assessment to the fore for biomarker development in future prospective, randomized trials, and emerging multi-omics classifiers.

Keywords: H&E; PBRM1; PD-1; RCC; TIL; biomarker; immunotherapy; irPRC; necrosis; pathologic response.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Biomarkers, Tumor
Carcinoma, Renal Cell*
Humans
Prognosis

Substances

Biomarkers, Tumor

Supplementary concepts

Clear-cell metastatic renal cell carcinoma

Abstract

Publication types

MeSH terms

Substances

Supplementary concepts

Grants and funding