Mass Cytometry in Translational Research: Session II

Understanding the immunosuppressive functions of cancer-associated fibroblasts in lung cancer

12:00–12:30 pm PDT

Presented By: Handan Xiang, PhD

Cancer-associated fibroblasts (CAFs) are activated fibroblasts that constitute the stromal component in the tumor microenvironment. Although CAFs have been shown to promote tumor growth and mediate resistance to chemotherapy, their roles and potential mechanisms by which they may contribute to immune suppression in lung squamous cell carcinoma remain largely unexplored. By leveraging patient genomic data and Imaging Mass Cytometry™, we identified a positive correlation between CAF and monocytic myeloid cell abundances as well as a significant spatial interaction between these two cell populations. In-depth analyses highlight a pivotal role of CAFs in regulating monocyte recruitment and differentiation into myeloid-derived suppressor cells.

Media smooth muscle cells reprogramming into mesenchymal stem cells drives aortic aneurysm formation

12:30–1:00 pm PDT

Presented By: Pei-Yu Chen, PhD

Using Imaging Mass Cytometry™ in combination with advanced single-cell RNA sequencing/AI data analysis, we demonstrated the existence of a disease-prone population of smooth muscle cells in the normal aorta. Under pathological conditions, this population of cells undergoes transformation into mesenchymal stem-like and macrophage-like cells and then differentiates in bone, cartilage and fat-forming cells. These cells replace normal cellular constituents of the aortic wall leading to the loss of the wall integrity and aneurysm development. The identification of disease-prone cell populations completely transforms our understanding of disease biology and opens the possibility of development of disease- and patient-specific therapies.

Unraveling the spatial distancing between immune compartments of COVID-19 tissues using IMC™

1:00–1:30 pm PDT

Hiranmayi Ravichandran, MS

Deciphering the immune landscape in the COVID-19 infected lung tissue is necessary to understand the host response to the pathogen. Using a panel of 34 antibodies, Imaging Mass Cytometry was applied on infected and noninfected lung specimens to present the preliminary evidence of tissue dynamics in its spatial resolution. By observing the lung at unprecedented detail, we gain better understanding of both SARS-CoV-2 infected lesions and the process of lung healing, which will enable and inform better management of the disease.

B cells and tertiary lymphoid structures (TLS) promote immunotherapy response

1:30–2:00 pm PDT

Presented By: Rafet Basar, MD

HLA-E and NKG2A as a novel immune checkpoint axis in bladder cancer

2:00–2:30 pm PDT

Presented By: Amir Horowitz, PhD

For more than 40 years, Mycobacterium bovis bacillus Calmette-Guérin (BCG) remains the only approved first-line therapy for treatment of high-risk non-muscle invasive bladder cancer (NMIBC), which represents ~70% of all diagnosed bladder cancer. BCG can induce durable responses, but a significant subset of patients will have recurrence or progression of disease. Immune checkpoint blockade (ICB) with anti-PD-1/PD-L1 antibodies has changed the treatment landscape for muscle-invasive bladder cancer (MIBC) and in BCG-resistant NMIBC and can induce durable responses unprecedented in the context of historical treatment approaches. In this study, we provide evidence of adaptive immune resistance unique to NMIBC, whereby IFN-g produced by activated, tumor-infiltrating NKG2A+ PD-1+ CD8 T cells enhances HLA-E and PD-L1 expression on tumors, resulting in an inhibitory interaction that may distinguish response to BCG therapy from recurrence of tumor. Using mass cytometry and Imaging Mass Cytometry (IMC™), we demonstrate that activated NK cells and CD8 T cells drive primary resistance through early IFN-g production that potently triggers elevated HLA-E and PD-L1 expression on tumors and progressive exhaustion due to chronic stimulation over the lengthy course of BCG therapy. Our preliminary findings provide a mechanism of BCG resistance and identify a novel approach to combination ICB targeting NKG2A and PD-L1 blockade.