TNBCs could be characterized as immune cold, compartmentalized, or mixed based on immune infiltration.

  • Major finding: TNBCs could be characterized as immune cold, compartmentalized, or mixed based on immune infiltration.

  • Approach: Multiplexed ion beam imaging measured in situ expression of 36 proteins in 41 patients with TNBC.

  • Impact: This multiplexed imaging approach uncovers compartmentalized tumors linked to improved survival.

Immune checkpoint blockade achieves responses in a variety of tumor types, including triple-negative breast cancer (TNBC). However, the tumor immune landscape is poorly understood, and adequate biomarkers are not available to identify the patients likely to benefit from immune checkpoint blockade. To characterize the tumor–immune microenvironment and identify determinants of response to immunotherapy, Keren and colleagues combined multiplexed ion beam imaging (MIBI), a method using secondary ion mass spectrometry to image antibodies tagged with isotopically pure elemental metal reporters in tissue sections, with time-of-flight mass spectrometry (TOF), to increase channel multiplexing and decrease acquisition times. This MIBI-TOF approach enabled imaging and quantification of 36 tumor–immune microenvironment proteins in situ in a tissue microarray of 41 patients with TNBC. An analysis pipeline including deep learning–based segmentation allowed automated image analysis to delineate immune cell populations. This method revealed heterogeneity in the composition of tumor–immune populations across individuals. Tumors could be divided into immune cold (with no immune cell infiltrate), mixed (with immune cells mixed with tumor cells), and compartmentalized (with immune cells spatially separated from tumor cells) tumors, subsets that were associated with different immunoregulatory protein expression patterns. The compartmentalized tumors were linked with increased survival compared with the mixed tumors. The use of MIBI-TOF to characterize the tumor–immune microenvironment in patients with TNBC provides insight into the spatial relationship between tumor and immune cells, and identifies immune phenotypes linked to survival. Further, this multiplexed imaging approach may be useful in guiding drug selection in patients with cancer.

Keren L, Bosse M, Marquez D, Angoshtari R, Jain S, Varma S, et al. A structured tumor-immune microenvironment in triple negative breast cancer revealed by multiplexed ion beam imaging. Cell 2018;174:1373–87.

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