News

The Cancer Research Institute has granted the Hudson Laboratory a two-year Technology Impact Award to advance the adoption of spatial T cell receptor (TCR) sequencing technology for the analysis of preserved tissue samples.

This initiative aims to deepen our understanding of T cell function and antigen specificity within the tumor microenvironment. T cells, vital components of the immune system, detect foreign and mutated proteins present in cancer cells. Spatial TCR sequencing allows the evaluation of T cell specificity and their spatial distribution within tissues, shedding light on how the tumor environment influences T cell function and their response to immunotherapy. By extending this technique to preserved tissue, the project seeks to investigate T cell activity and location within tumors using a wider range of available samples. This advancement would lead to valuable insights into the distribution and behavior of T cell clones within the tumor microenvironment, aiding the evaluation of disease progression and response to immunotherapy.

New Hudson Lab research was published today in Cell Reports Medicine!

In this report, we analyzed two brain tumors from the same patient – one tumor had received radiation, and the other was untreated. We performed advanced sequencing experiments to analyze gene and protein expression on more than 45,000 single cells from the two tumors and the patient’s blood immune cells. Because the two tumors are from the same patient, we could compare T cell receptor sequences – which are barcodes that track antigen-specific cells within a person – between the two samples.

Our results show that radiation is associated with dramatic immune changes in the tumor microenvironment. Despite similar mutational profiles between the untreated and irradiated samples, tumor-enriched T cells are nearly entirely depleted following radiation. These tumor-specific cells are instead replaced by T cells from the circulation, which are unlikely to contribute to tumor-specific immunity. Radiation also caused a depletion of tumor-associated macrophages and an influx of pro-inflammatory monocytes from the circulation. These findings indicate that radiation may deplete beneficial cells that contribute to anti-tumor immunity.

Read the full paper here.

We recently presented our work on spatial T cell receptor sequencing at the 10x Genomics Spatial Biology Symposium in Boston! You can check out the recording on demand here.

We have a new publication in Cancer Cell! In this perspective article, we discuss the role of various -omics technologies in studying T cells within the tumor microenvironment. In particular, we focus on the opportunities these techniques present to deepen our understanding of T cell biology and also describe the challenges that arise in the interpretation and analysis of these experiments.

Our work describing a new assay for antibody epitope mapping was published today in Cell. This work was a collaboration with the Ortlund Lab at Emory University.

New SARS-CoV-2 mutations are emerging continually, threatening not only to evade immune responses but also to escape binding of antibodies used in antigen tests (also known as rapid tests) to detect COVID-19 infection. In this work, we describe a new method to identify SARS-CoV-2 mutations that escape commonly-used antigen tests.

Most antigen tests detect the SARS-CoV-2 nucleoprotein. To map epitopes of anti-nucleoprotein antibodies, we induced nucleoprotein expression on the surface of cells by adding a secretion leader sequence to the N-terminus and a transmembrane domain to the C-terminus. We then created a deep mutational library that expressed every possible single nucleoprotein mutation. By incubating this library of surface-expressed nucleoprotein with antibodies used in rapid tests and sorting cells without antibody binding, we could identify every single mutation that eliminated nucleoprotein detection by rapid test antibodies.

The results from this assay showed that current variants of concern are unlikely to evade currently-available antigen tests. Additionally, these data provide a useful resource for predicting the detectability of future SARS-CoV-2 variants with antigen tests. Finally, this method is generalizable to map interaction and functional surfaces of proteins in a wide variety of contexts.

Our protocol for localization of T cell clones using the Visium platform is published in STAR Protocols. This protocol is a step-by-step guide on how to use a popular spatial transcriptomics platform to visualize the location of antigen-specific T cells directly within tissue. See our recent work in Cell Reports Medicine for our implementation of this technique in brain tumors.

The Cancer Prevention and Research Institute of Texas (CPRIT) has awarded a $2 million grant to the Hudson Lab! This five-year award will fund research in the laboratory to characterize CD8+ T cell responses in human tumors and develop new immunotherapies to improve immune responses to cancer. Read more here.

Our work describing the CD8+ T cell infiltrate of brain metastases is published today in Cell Reports Medicine! We show that metastatic brain tumors harbor lots of T cells, making them excellent targets for immunotherapy. Our work is also the first to use spatial TCR sequencing, allowing us to track individual T cell clones within tumor tissue! See also Emory University’s press release here.