EIKCS 2021: The Role of the Tumor Microenvironment in Renal Cancer

(UroToday.com) The European International Kidney Cancer Symposium 2021 virtual meeting included a basic science session and a presentation by Dr. Barbara Seliger discussing the role of the tumor microenvironment in renal cancer. Dr. Seliger suggests that the hallmarks of renal cell carcinoma are sustained angiogenesis and evading immune surveillance. There are several immune escape strategies of renal cell carcinoma, including based on tumor cells, the micro milieu, and the periphery, as highlighted by Dr. Seliger in the following figure:

DeRosa_Seliger_1.png

Additionally, there are several approaches for analyzing the tumor microenvironment, including:

  • Expression and localization 
    • Mass cytometry, immunohistochemistry, and multi-color flow cytometry
    • Transcriptome analysis and single cell RNA seq, spatial transcriptomics, and in silicoanalyses and bioinformatics
  • Models and function – MCTC and co-culture, slice culture, and organoids

There is significant heterogeneity of the composition of the tumor microenvironment in renal cell carcinoma. This includes the mesenchymal compartment (ie. fibroblasts, adipocytes), the immunological compartment (ie. NK cells, B cells, microphages, T-reg cells, and B-reg cells), and the vascular compartment (ie. hypoxia). 

Dr. Seliger notes that there are major characteristics of the tumor microenvironment of clear cell RCC, which are as follows:

  • Heterogeneic inter- and intra-tumoral micromilieu 
  • Angiogenic features of the microvasculature
  • Spatial organized network of high-levels of infiltration with different (immune) cell subpopulations
  • Modulation of all aspects of tumor development and therapy resistance 
  • Subcategorization of different immune relevant renal cell carcinoma phenotypes based on RNA seq and CyTOF data

Dr. Seliger also highlighted several biomarker signatures with regards to prognostication of renal cell carcinoma:1

  • Phenotype I (high angiogenesis and altered metabolism): immune-silent clear cell RCC, low frequency of immune T cell infiltration, similarity of TILs to non-malignancy kidney resident TILS, and non-activated tumor lymphocytes
  • Phenotype II (immune-regulated clear cell RCC): reduced T cell clonality, reduced cytotoxicity, higher risk of relapse
  • Phenotype III (immune activated clear cell RCC): high frequency of activated CTL

The prognostic and predictive relevance of major tumor microenvironment components are as follows: 

DeRosa_Seliger_2.png

Dr. Seliger concluded her presentation highlighted aspects of the tumor microenvironment in renal cell carcinoma with the following take home messages:

  • There is a heterogeneic, complex and dynamic inter- and intra-tumoral immune cell composition 
  • Association of high levels of diverse immune suppressive cells and non-functional CD8+ T cells with worse prognosis
  • There is clinical relevance in that the selection of renal cell carcinoma patients for therapies can be based on tumor immunogenicity, tumor infiltrating (immune) cell repertoire, and the cellular composition of peripheral blood cells

 

Presented by: Barbara Seliger, MD, PhD, Institute of Medical Immunology. Martin Luther University Halle-Wittenberg, Halle, Germany

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md during the 2021 European International Kidney Cancer Symposium (EIKCS), April 23-24, 2021


References:

  1. Vuong L, Kotecha RR, Voss MH, et al. Tumor Microenvironment Dynamics in Clear-Cell Renal Cell Carcinoma. Cancer Discov. 2019 Oct;9(10):1349-1357. 
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