Project 1: Identifying recruited CD8+ T cells in tumors and the pathways engaged to drive T cell dysfunction during tumor progression

CD8+ T cell responses are shaped by multiple factors, including duration of antigenic stimulation and the local microenvironment. Moreover, my recent work showed that recruitment of DLN CD8+ T cells is critical for maintaining CD8+ T cells in tumor-bearing lungs...

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Project 1: Identifying recruited CD8+ T cells in tumors and the pathways engaged to drive T cell dysfunction during tumor progression

CD8+ T cell responses are shaped by multiple factors, including duration of antigenic stimulation and the local microenvironment. Moreover, my recent work showed that recruitment of DLN CD8+ T cells is critical for maintaining CD8+ T cells in tumor-bearing lungs.

This project will seek to address the following questions.

(1) How long doCD8+ T cells persist and how rapidly are they replaced?

(2) What programs are engaged in the TME?

(3) How do these tissue-specific programs contribute to driving dysfunction?

The major goal is to define CD8+ T cell longevity in tumors and identify the pathways that are engaged in the hours, days and weeks after arrival. A better understanding of temporal and spatial contributors to T cell dysfunction will be critical for identifying targetable pathways to boost CD8+ T cell responses in
tumors.

Project 2: Dissecting the role of metastasis in modulating the CD8+ T cell response

Metastasis is a process whereby cancer cells migrate into blood or lymphatics and engraft elsewhere in the body. Lung adenocarcinoma patients with distal metastatic disease have a poor prognosis, with a significantly decreased 5-year-survival of 7% compared to 65% for patients with localized lung lesions. However, little is known about how the T cell response changes during and after metastasis. The project will address the following questions.

(1) What happens to the functional reservoir of tumor-specific CD8+ T cells in the DLN after metastatic spread and invasion?

(2) Are the programs engaged in tumor-specific CD8+ T cells different in primary versus metastatic lesions?

The major goal of this project is to understand how metastasis alters the anti-tumor CD8+ T cell response. A better understanding of the CD8+ T cell response in metastasis will provide insights and targets for future immunotherapies.

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