Harvard Catalyst Profiles

Department of Defense Awarding Office: USAMRAA

Terminally Exhausted CD8+ Tumor-Infiltrating Lymphocytes and M2-Like Macrophages as Biomarkers of Resistance to First-Line Anti-PD-1 Therapy in Metastatic RCC

Role Description: We propose a whole slide multiplex immunofluorescence characterization of T cell exhaustion and of hypothesized modifying factors in the microenvironment of kidney cancer. Roughly 70% of patients presenting a metastatic clear cell renal cell carcinoma (mccRCC) treated with anti-PD-1 do not benefit from therapy due to upfront or secondary resistance. Prior studies unveiled the fact that a high density of non-exhausted T cells (CD8+PD-1+TIM3-LAG3-) was predictive of response to anti-PD-1 therapy in previously treated patients with mccRCC. Despite this, most of the biology underlying immune checkpoint blockade remains unknown, and no biomarker is available in clinical practice to guide the prescription of these therapies. We will study the issue from a new angle with the goals of better understanding the biology, to provide markers of resistance to treatment, and identifying potential new therapeutic targets.

Role: principal investigator