What Dictates T Cell Response in Cancer Checkpoint Treatment?

What Dictates T Cell Response in Cancer Checkpoint Treatment?

Table of Contents

Bioinformatics Analytics

By Jane Cook
March 7, 2022

Cancer Immune Checkpoint Therapy

What are the molecular changes that occur inside a tumor during checkpoint therapy? A recent paper in Nature Medicine harnessed single-cell RNA sequencing (scRNA-seq) to map what happens inside a breast cancer tumor during anti-PD1 treatment.

Immune checkpoint blockade (ICB) has emerged as an extremely successful strategy for cancer therapies. Treatments like pembrolizumab (Keytruda) and atezolizumab (Tecentriq) utilize the PD-L1 biomarker to identify the patients most likely to respond well to the treatment, and function by reactivating the T cells in the body’s immune system to target cancer cells.

The Challenge of Breast Cancer

However, for some cancer types, PD-L1 is an insufficient biomarker to robustly predict patient outcomes. One example of this is breast cancer, which has several heterogenous subtypes, from triple-negative breast cancer (TNBC) to human epidermal growth factor receptor 2-negative (HER2-) breast cancer.

Although ICB treatment has shown positive results overall across breast cancer subtypes, there is still a significant proportion of patients that do not respond. Thus, this research team set out to identify further markers of what is happening inside the tumor under different treatment conditions and the resulting outcomes for the patient.

scRNA-Seq Reveals Distinct Immune Cell Phenotypes

What they found was a significant variation in the ability of the cancer-killing T cells to clearly expand in response to the anti-PD1 treatments. Tumors that had higher levels of certain dendritic cells, CCR2+ and MMP9+ macrophages, and expression of MHC class I and II correlated positively with T cell expansion. Tumors that had higher proportions of undifferentiated T cells and inhibitory macrophages, on the other hand, showed a negative correlation with T cell expansion.

These data add a new layer to understanding the response to ICB therapy by further characterizing the immune cell phenotypes present in the tumor and their effects on treatment response. This opens avenues to potential new biomarkers for companion diagnostics and predicting patient responses, and reinforces the utility of scRNA-seq for these kinds of analyses and discoveries.

Outsourcing Bioinformatics Analysis

Interpreting single-cell RNA-seq data is a challenging computational and bioinformatic task. Outsourcing your bioinformatic analysis to experts like our team at Bridge Informatics helps eliminate common challenges with these projects. If you’re interested, book a free discovery call with us today to discuss your project needs.

Jane Cook, Journalist & Content Writer, Bridge Informatics

Jane is a Content Writer at Bridge Informatics, a professional services firm that helps biotech customers implement advanced techniques in the management and analysis of genomic data. Bridge Informatics focuses on data mining, machine learning, and various bioinformatic techniques to discover biomarkers and companion diagnostics. If you’re interested in reaching out, please email [email protected] or [email protected].



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