New Technique May Predict Response to Neoadjuvant Immunotherapy in Certain Patients With Breast Cancer

A novel technology that allows for the study of protein expression at the single-cell level and the location of the cells within the tumor microenvironment (TME) was proven feasible, according to results presented at the San Antonio Breast Cancer Symposium. The investigators found this technology provided information on the benefit of adding the immune checkpoint inhibitor atezolizumab to chemotherapy as a neoadjuvant treatment for patients with early high-risk and locally advanced triple-negative breast cancer (TNBC).

“We are experiencing a revolution in the technologies available for characterizing the molecular complexity of tumors,” said presenter Giampaolo Bianchini, MD, head of the Breast Cancer Group in the Department of Clinical Oncology at IRCCS Ospedale San Raffaele, Milan, in a press release. “Among these, imaging mass cytometry allows us to collect unprecedented information about the heterogeneity of tumors and their surrounding microenvironment.”

Imaging mass cytometry (IMC) allows investigators to simultaneously analyze more than 40 markers in a single tissue section to identify the set of proteins present on individual cells while accounting for their precise location within the tissue.

According to the investigators, IMC combines the principles of flow cytometry, which analyzes single cells or particles as they flow by 1 or more lasers, and mass spectrometry, which identifies the molecules present in a sample by accurately measuring their mass.

Emerging evidence suggests TNBC tumors are infiltrated with mononuclear cells and lymphocytes, and combining immune checkpoint inhibition with chemotherapy has demonstrated a significant benefit for high-risk TNBC patients, according to the researchers. This led to the FDA approval of pembrolizumab in combination with chemotherapy as neoadjuvant therapy in this setting.

“Unfortunately, one size does not fit all patients and it is possible that some of them may have responded to chemotherapy alone, while others who originally benefited from immunotherapy will eventually relapse. In addition, although immunotherapy is overall well tolerated, some rare but potentially serious immune-related side effects have been reported,” Bianchini said in the release. “For these reasons, biomarkers are urgently needed to help us identify the patients who will benefit the most from the addition of immunotherapy—potentially leading to chemotherapy de-escalation or chemo-free strategies, and those who will do well just with chemotherapy.”

For this reason, the investigators studied whether IMC could assist in identifying ideal candidates to benefit from immunotherapy. Performing IMC analysis in the phase 3 NeoTRIPaPDL1 trial, the investigators successfully analyzed 43 proteins expressed on more than 1 million single cells identified in tissue samples collected through pre-treatment biopsies from 243 patients.

This approach revealed the potential predictive role of the density of certain cell populations, with a high density of antigen presenting cells with high expression of PD-L1 and the immunosuppressive molecule IDO and of epithelial cells with high expression of the CD56 neuroendocrine marker being associated with higher pCR in patients who received atezolizumab plus chemotherapy, but not in patients who only received chemotherapy.

“Our results demonstrated that spatial data on the interactions among specific cells in the TME might be very informative about the benefit provided by an immune checkpoint inhibitor such as atezolizumab in addition to chemotherapy,” Bianchini said in the release. “This type of information can only be provided by technologies that allow us to simultaneously characterize the single cells and their spatial localization with precision.”

REFERENCE

Single-cell spatial analysis may help predict response to neoadjuvant immunotherapy in triple-negative breast cancer [news release]. EurekAlert; December 7, 2021. Accessed December 8, 2021. https://www.eurekalert.org/news-releases/937177