Characterization of Immune Cells in the RCC Tumor Microenvironment

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Overall, 3.5 million cells were analyzed and 17 major tumor-associated macrophage phenotypes were identified.
Overall, 3.5 million cells were analyzed and 17 major tumor-associated macrophage phenotypes were identified.

The phenotypes of immune cells present in the tumor microenvironment and those associated with progression-free survival (PFS) were characterized in a study published in Cell.1

Macrophages and T cells are known components of the tumor microenvironment, but their exact role remains unknown. The purpose of this study was to characterize the phenotypes of these immune cells and determine their effect on clinical outcomes in clear cell renal cell carcinoma (RCC).

The study performed large-scale mass cytometry of 73 tumor samples from patients with clear cell RCC of all grades and 5 samples from matched healthy kidneys.

“Mass cytometry enables the quantification of more than 50 readouts at the single-cell level by combining metal isotope-labeled antibodies with mass spectrometry detection,” wrote the authors.

The analysis included 2-dimensional mapping and algorithms to identify overlapping characteristics and subsets of immune cells from the tumor samples.

Overall, 3.5 million cells were analyzed and 17 major tumor-associated macrophage phenotypes were identified.

There was broad expression of PD-1 by CD8+ T cells, but TIM-3, CTLA-4, and 4-1BB were expressed only by a small subset of PD-1+ clusters, suggesting that therapeutic targeting of PD-1 may be more effective. The authors also identified CD38 as a potential marker of T cell exhaustion.

Subsets that had higher expression of M-11 and/or M-13 and low levels of M-5 were associated with shorter PFS.

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According to the authors, the findings of this study represent an immune cell atlas that “will provide a valuable resource to accelerate research…in improving immunotherapies and supporting the development of novel treatments.”

Reference

  1. Chevrier S, Levine JH, Zanotelli VR, et al. An immune atlas of clear cell renal cell carcinoma. Cell. 2017;169:736-49. doi: 10.1016/j.cell.2017.04.016

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