Triple-negative breast cancer, a ‘special’ imaging to predict immunotherapy response

Imaging with mass cytometry (IMC) could provide relevant indications to better understand triple-negative breast cancer and evaluate the possible benefits of immunotherapy, as showed by data from a study by the Michelangelo Foundation, presented during the opening session of the San Antonio Breast Cancer Symposium 2021 by Giampaolo Bianchini of the Department of Medical Oncology – San Raffaele Hospital in Milan and Scientific Coordinator of traslational studies on breast cancer in Michelangelo Foundation.

Immunotherapy with immune checkpoint inhibitors, such as anti-PD-L1, is effective in early and advanced triple-negative breast cancer, but only a minority of patients respond: understanding who can benefit most from treatments would therefore be very helpful and to do this, researchers from the Michelangelo Foundation analyzed samples from patients enrolled in the NeoTRIP study through IMC. Designed and conducted by the Michelangelo Foundation, NeoTrip is a phase III clinical trial to evaluate the clinical benefits of adding a neoadjuvant immunotherapy with atezolizumab to chemotherapy with nab-paclitaxel and carboplatin in patients with high risk or locally advanced triple-negative breast cancer; the researchers used IMC on 243 samples, where the tumor microenvironment and the expression of 44 different proteins were also assessed in pre-treatment biopsies.

Analysis with IMC, profile at one micron spatial resolution, identified over one million single cells that could be grouped into 37 different cell types with distinct phenotypes; the investigation showed the great tumor heterogeneity and the differences in the tumor microenvironment, while the comparison with the expression of specific proteins allowed to identify some ‘markers’ of the pathological complete response. For example, above median expression of GATA3 and CD20 in  tumor microenvironment, HLA-DR in epithelial cells, and Ki67 in the microenvironment and epithelial cells was associated with a greater than 10% increase in pathological complete response in patients treated with atezolizumab compared to the other arm; relevant data were obtained from the analysis of the phenotypes of neuroendocrine epithelial cells and antigen presenting cells, where the above median expression of PD-L1 / IDO and CD56 + was associated with 64.6% of pathological complete response in patients of the atezolizumab arm. Data show that IMC is feasible in a large trial and allows a more in-depth evaluation of tumor heterogeneity, with a single-cell spatial resolution: a bulk evaluation of genes and proteins expression is not as predictive, because it does not the cell compartment of expression. IMC could therefore provide relevant and predictive information to identify patients who can benefit most from immune checkpoint inhibitors.