Publication in Clinical Cancer Research: IsoPlexis’ Single-Cell Proteomics Reveals Unique Cell Subsets Associated with Improved Outcomes in Triple Negative Breast Cancer

  • In a study published in Clinical Cancer Research, researchers used IsoPlexis’ single- proteomics to identify an association of upregulated polyfunctional CD8+ PD-1HI cell subsets in blood with increased immune responses of patients with triple negative breast cancer (TNBC) to neoadjuvant chemotherapy (NAC). These polyfunctional cells had an elevated pattern of anti-tumor associated protein secretions and were markedly promoted by NAC in TNBC patients compared to non-TNBC patients.
  • In addition, these peripheral polyfunctional CD8+ PD-1HI cells showed a significant increase of cytotoxicity in TNBC patients in response to NAC. IsoPlexis’ single-cell proteomics showed that NAC treatment was able to increase T cell functionality in TNBC patients with RD, greatly improving outcome.
  • IsoPlexis’ single-cell proteomics demonstrates a great upregulation of polyfunctional PD-1HI T cell subsets in TNBC patients who are uniquely sensitive to the immunomodulatory effects of NAC, providing a potential peripheral prognostic biomarker and mechanistic insights for chemotherapy combinations with immunotherapy in patients with the most aggressive TNBC.

Increased Polyfunctionality of CD8+ T Cells in Triple Negative Breast Cancer Tumors After Neoadjuvant Therapy Predicts Effectiveness of Combination Treatment

In a paper recently published in Clinical Cancer Research, researchers at Vanderbilt used IsoPlexis’ single-cell proteomics technology to characterize the immune response before and after neoadjuvant chemotherapy (NAC) in breast cancer tumors, specifically triple negative breast cancer tumors (TNBCs). The current treatment for this type of tumor affects both the local and systemic immune responses but this has not been completely characterized. These types of tumors typically benefit from additional therapy, and recently chemotherapy in combination with a PD-L1 targeted therapy, atezolizumab, was approved to treat TNBC based on the results of a Phase III clinical trial. When pembrolizumab, an anti-PD-1 monoclonal antibody, was added to NAC, it was shown to significantly enhance pathological complete response (pCR) rates in TNBC.1 Researchers at Vanderbilt used IsoPlexis’ highly multiplexed single-cell technology to analyze the immune response in TNBC breast tumors and expand the previously limited studies to analyze the immune response to NAC.

Generally, TNBC patients who receive NAC tend to correlate with pCR when they have high levels of stromal tumor-infiltrating lymphocytes (sTILs) in their biopsies pre-treatment, however, patients with residual disease (RD) often require additional treatment. Researchers Axelrod et al. found that “even when considering only TNBC, quantification of sTILs is an imperfect biomarker, which does not precisely inform on the immune-biology of the tumor.”1 So, while previous studies have shown that tumors treated with NAC that had an elevated expression of PD-L1 were associated with an improved response, this was only shown in a small number of TNBCs and did not test the long-term outcomes for RD patients. This Clinical Cancer Research study seeks to address this knowledge gap by analyzing 83 breast tumors, 44 of which are TNBCs, from patients with RD using IsoPlexis’ technology.1

“Existing clinical data indicate that chemotherapy combinations with immunotherapy demonstrate enhanced efficacy compared to chemotherapy alone. However, these results suggest a growing need to better understand how chemotherapy modulates the tumor-immune microenvironment….Examining immune-related signatures locally and systemically may serve as biomarkers of patients likely to benefit from additional immunotherapeutic approaches.”1

IsoPlexis’ Unique Single-Cell Proteomics Identifies Highly Functional Cell Subset Correlating to Improved Outcome in Triple Negative Breast Cancer

Researchers Axelrod et al. used IsoPlexis’ highly multiplexed single-cell proteomics to reveal a unique highly functional PD-1HI peripheral T cells subset, specifically the CD8+ T cell subset, had high functional capacity due to their ability to secrete multiple cytokines after being activated. After NAC treatment, this highly functional subset of cells increased in polyfunctionality.1 These researchers were able to confirm that TNBC is uniquely sensitive to the immunologic effects of NAC and that this change is associated with improved outcomes.

clinical cancer research

Figure adapted from Axelrod ML, et al. “Changes in peripheral and local tumor immunity after neoadjuvant chemotherapy reshape clinical outcomes in patients with breast cancer.” Clinical Cancer Research 2020.

IsoPlexis’ single-cell proteomics revealed unique functional cell subsets and showed that NAC treatment was able to increase T cell functionality in TNBC patients with RD, greatly improving outcome. Read the full article, “Changes in peripheral and local tumor immunity after neoadjuvant chemotherapy reshape clinical outcomes in patients with breast cancer” here.

Reference:

  1. Axelrod ML, et al. Changes in peripheral and local tumor immunity after neoadjuvant chemotherapy reshape clinical outcomes in patients with breast cancer. Clinical Cancer Research
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