Immunotherapeutic approaches are changing treatment paradigms for several types of cancer. However, to fully realize the potential of this approach, a deeper understanding of the immune cell ecosystem in the tumour microenvironment is required. Now, two studies in Cell present mass-cytometry-based multiscale immune profiling strategies that allow unprecedented insights into the immune cell subsets in tumours and how tumours influence their composition.
To identify tumour-driven immune changes, Merad and colleagues examined the phenotype of different subsets of innate and adaptive immune cells, as well as cytokine and chemokine production, in untreated patients with early stage lung adenocarcinoma. To compare the immune microenvironment in tumours, adjacent normal tissue and blood, the authors developed a barcoding method that allowed simultaneous single-cell analysis of cells from different tissues. This strategy was complemented by a new immunohistochemical tissue-profiling method to examine the spatial distribution of immune cells in the tumour, as well as by single-cell transcriptomic analysis of tumour-infiltrating myeloid cells (TIMs).
The overall result was a detailed atlas of the tumour immune landscape, showing significantly altered T cell and natural killer (NK) cell compartments, as well as characteristic changes in TIM subsets in tumour compared with normal adjacent tissue. These included a distinct transcriptional signature in tumour-associated macrophages (TAMs), which indicated an immunosuppressive phenotype. Strikingly, these changes were independent of tumour stage, suggesting that patients with early stage cancer may already benefit from immunotherapeutic anticancer approaches.
Using a similar strategy, Bodenmiller and colleagues mapped the immune landscape of tumours in patients with clear cell renal cell carcinoma, with the aim of correlating immune cell compositions with clinical features. In particular, their study focused on the characterization of different subsets of T cells and TAMs, and identified 22 T cell phenotypes and 17 TAM phenotypes in the tumour microenvironment. This was followed by a systematic correlation analysis to gain insight into the relationships between the immune cell subsets, and a correspondence analysis that examined the relationship between immune cell subsets and clinical parameters.
“the structure of the immune landscape is a powerful predictor of patient outcome”
The authors found that the presence of some CD8+ T cell and TAM phenotypes was mutually exclusive, and they detected an unexpected diversity of PD1+ T cells in tumours. The frequency of different populations of TAMs showed wide variability among patients, and a particular TAM phenotype was associated with the presence of specific populations of exhausted CD8+ and regulatory T cells. Moreover, they were able to show that the structure of the immune landscape is a powerful predictor of patient outcome. These studies provide a wealth of insights into the interplay between immune and tumour cells, which may guide treatment decisions and allow the design of new anticancer strategies.
Lavin, Y. et al. Innate immune landscape in early lung adenocarcinoma by paired single-cell analyses. Cell http://dx.doi.org/10.1016/j.cell.2017.04.014 169, 750–765 (2017)
Chevrier, S. et al. An immune atlas of clear cell renal cell carcinoma. Cell https://www.ncbi.nlm.nih.gov/labs/articles/28475899/ 169, 736–749 (2017)
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Flemming, A. Immune atlas sheds light on anticancer responses. Nat Rev Immunol 17, 347 (2017). https://doi.org/10.1038/nri.2017.59