The Hudson Laboratory

We are thrilled to congratulate graduate student Amanda Xia on being awarded an F30 fellowship grant from the National Institute of Allergy and Infectious Diseases (NIAID) to support her doctoral research. Amanda is a student in Baylor’s MD/PhD program, and this four-year, $198,000 award will fund her investigation into how CD8+ T cells – the immune system’s front-line killers of virus-infected and tumor cells – carry out their work, and how that process breaks down in chronic settings like long-term viral infections and cancer.

When the immune system faces a persistent threat, CD8+ T cells can lose their ability to effectively eliminate infected or cancerous cells – a process known as exhaustion. Amanda’s research aims to uncover the molecular mechanisms that drive this loss of function, with the goal of identifying new ways to restore or enhance T cell killing capacity. A deeper understanding of these processes could open new doors for improving immunotherapy outcomes for patients with chronic infections and cancer.

We are incredibly proud of Amanda and grateful to NIAID for their support of this work!

We are thrilled to share that our lab’s work on spatially resolved T cell profiling in head and neck cancer has been published in Science Immunology!

In this study, led by postdoctoral scientist Dr. Kelli McCord, we developed a new approach to visualize where specific T cell clones are located within tumors – at single-cell resolution – and applied it to head and neck squamous cell carcinoma (HNSCC), a disease responsible for nearly 400,000 deaths each year that remains difficult to treat with immunotherapy.

To do this, we combined high-parameter spectral flow cytometry and single-cell RNA and TCR sequencing on 27 patients with HNSCC. We then used the Xenium spatial transcriptomics platform and designed patient-specific probes targeting individual T cell receptor sequences, allowing us to map the precise location of specific T cell clones while simultaneously measuring their gene expression in intact tumor tissue.

Our results revealed that T cells with more robust cancer-fighting potential clustered in immune-rich niches, while exhausted T cells were more broadly dispersed in tumor-dense regions. Strikingly, cells sharing the same T cell receptor — and therefore recognizing the same target — could adopt fundamentally different functional states depending on where they were located in the tumor. This spatial heterogeneity was not captured by conventional approaches like flow cytometry or single-cell RNA sequencing alone, suggesting that local environmental cues in the tumor — not clonal identity alone — play a dominant role in shaping T cell fate. They also reveal substantial differences in immune architecture across patients that may help explain why some respond to immunotherapy while others do not.

We are particularly grateful to our clinical collaborators, to the patients who donated samples, and to the many core facilities and funding sources that made this work possible.

We are excited to share our lab’s latest publication in Cell Reports! In this study, led by graduate student Sean Hyslop, we uncover a critical role for the surface receptor CD7 in helping exhausted CD8⁺ T cells persist during chronic infection.

Exhausted CD8⁺ T cells develop when the immune system is subjected to prolonged stimulation, such as in cancer or chronic viral infections. While these cells can initially control disease, over time they lose function and many undergo apoptosis (a form of programmed cell death). This process – known as exhaustion – limits their therapeutic potential. Understanding what allows some exhausted T cells to survive is essential for improving immunotherapy.

Using mouse models, we discovered that CD7 expression steadily increases as CD8⁺ T cells become exhausted, reaching its highest levels on a specialized subset found in the liver. When CD7 was deleted, these cells were lost over time due to increased susceptibility to apoptosis. Single-cell RNA sequencing confirmed that CD7-deficient T cells showed broad gene expression changes, including reduced survival pathways.

Importantly, this biology extends to people: tumor-infiltrating T cells from patients with head and neck cancer also upregulate CD7, particularly in a population enriched for tumor-specific exhausted cells. This suggests that CD7 provides a conserved survival signal relevant to both chronic infection and cancer.

Together, these findings identify CD7 as a new regulator of exhausted T cell persistence and highlight how tissue-specific environments shape immune cell fate. By supporting the survival of exhausted T cells, CD7 may represent a novel target for therapies aimed at enhancing immune responses in chronic infections and cancer.