Using IsoPlexis’ Single-Cell Polyfunctional Analysis to Accelerate Breast Cancer Therapies

Breast cancer is one of the most commonly diagnosed forms of cancer – staggeringly, it is estimated that 1 in 8 women will be diagnosed with the disease in their lifetime. Treatment options for breast cancer include surgery, radiation, chemotherapy, and more recently, targeted therapies and immunotherapies. Targeted therapies, which are directed at proteins present on cancer cells, and immunotherapies, which harness the patient’s own immune system, have shown great promise in treating breast cancer and other solid tumors. Though the treatment landscape for breast cancer has expanded in recent years, there is still a critical need for the development of new approaches because the disease is ranked as the second leading cause of cancer death in woman at the current moment, just behind lung cancer. 

Cellular immune for immunotherapy development

The development of targeted therapies and immunotherapies for breast cancer and other solid tumors requires further interrogation of the interaction between immune cells and tumor cells, which can be accomplished through immune profiling. Unlocking this deep level of insight requires careful examination of the functional proteomes of individual immune cells through multiplexed cytokine analysis at the single-cell level.

IsoPlexis’ IsoCode Single-Cell Secretome solution allows researchers to easily see how each immune cell is contributing to the immune response through analyzing polyfunctionality, the ability of a cell to secrete 2 or more cytokines. This type of data empowers researchers to gain functional insight at single-cell resolution to identify cellular subsets that correlate to in vivo results and are predictive of key biomarkers such as clinical response.

Case Study: T cell polyfunctionality provides mechanistic insight into immunologic effects of chemotherapy in triple negative breast cancer

In a study published in Clinical Cancer Research, researchers sought to better understand the effects of neoadjuvant chemotherapy (NAC) on the immune system – specifically, how NAC affects the tumor microenvironment in triple negative breast cancer (TNBC). TNBC has proven challenging to treat as the tumor cells lack receptors for estrogen and progesterone, and exhibit low expression of HER2, making the cells difficult to target. As the combination of NAC plus immunotherapies has demonstrated more favorable outcomes in the clinic, it is important to identify the molecular mechanisms that can be harnessed to fine tune existing and new treatment paradigms.

The researchers used IsoPlexis’ single-cell immune profiling capabilities to compare PBMCs in donors with TNBC to PBMCs from both an estrogen receptor-positive (ER+) breast cancer donor and an ER+HER2+ breast cancer donor undergoing NAC to investigate the effects of NAC across different types of breast cancers.

They revealed that peripheral T cell subsets with high programmed cell death 1 expression (PD-1HI) exhibited polyfunctionality, more greatly pronounced in the CD8+ T cell subsets, after treating with NAC. Furthermore, CD8+ T cell polyfunctionality was increased following NAC treatment in the TNBC group where, conversely, the other groups had a reduction or plateau in polyfunctionality. Characterization of the cytokines secreted from the polyfunctional CD8+ PD-1HI T cells showed an elevated pattern of antitumor-associated cytokines. By revealing the upregulation of TNBC T cell subsets that are responsive to NAC, IsoPlexis’ single-cell functional phenotyping provides mechanistic insights for chemotherapy combinations with immunotherapy to treat TNBC.

Case Study: Cytokine analysis reveals a key driver of breast cancer cell migration and metastasis

In addition to single-cell functional analysis, IsoPlexis’ CodePlex solution enables researchers to perform multiplexed cytokine analysis on bulk samples. Researchers used this platform to investigate the mechanisms underlying breast cancer cell migration that can lead to metastasis. In a study published in Nature Communications, the researchers described studying the secretome of a breast cancer cell line using IsoPlexis’ multiplexed bulk protein analysis platform.

They observed that IL-6 and IL-8 were both highly secreted and that the levels increased with cell density, unlike other cytokines associated with pro-inflammatory activity. These findings and subsequent experiments indicated that IL-6 and IL-8 act together to drive cell migration. Using IsoPlexis’ CodePlex solution to analyze an array of secreted cytokines, the researchers were able to identify a new mechanism of breast cancer metastasis, one that can be targeted to lead to better treatment outcomes.

Single-Cell Cytokine Analysis Reveals Mechanisms of Immune Response in Cancer Treatment

There is a critical need for the development of new therapies and therapeutic combinations to improve the treatment landscape for breast cancer and other solid cancers. Through immune profiling, researchers are empowered to identify the functional phenotypes of immune system to detect cells that are driving both progression and response. Functional analysis provides a unique data layer that can be harnessed for accelerated therapeutic development to combat the world’s toughest diseases.

 

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