Alex Tsankov, PhD

Lung adenocarcinoma (LUAD) with TP53 mutations is an aggressive cancer that suppresses the immune system. Approximately half of LUAD cases have TP53 mutations, where to date no targeted therapies exist for this mutation, resulting in poor outcomes. Our proposed research explores how TP53 mutations alter immunosuppressive interactions between cancer and immune cells involving the proteins PVR and TIGIT. Using emerging spatial transcriptomics technologies, we will map where these interactions occur within tumor tissues, providing novel spatial and cellular context. We will also test new treatment strategies by disrupting PVR-TIGIT interactions in combination with other existing immunotherapies. Additionally, we will assess the therapeutic potential of these new combination treatments using in-vitro models that mimic patient tumors. By combining cutting-edge spatial technologies and in vitro culture modeling, this study aims to identify new treatment strategies for patients with TP53-mutant LUAD and promises to ultimately improve outcomes and personalize care for these patients.

American Lung Association Susan Rappaport Lung Cancer Discovery Award 

Update: Our work focuses on lung adenocarcinoma, the most common type of lung cancer, and specifically on tumors with mutations in the TP53 gene, one of the most frequently altered genes in cancer and a key driver of poor outcomes. By combining cutting-edge genomic technologies, computational analysis and laboratory experiments, we are uncovering new ways to better target these aggressive tumors. Our work lays a strong foundation for understanding how TP53 mutations reshape the tumor microenvironment and create vulnerabilities that can be targeted therapeutically. By integrating spatial genomics, computational modeling and functional experiments, we have validated key immune-suppressive interactions directly within human tumors; identified structured cellular niches that promote tumor progression; discovered regulatory mechanisms driving immune checkpoint expression; and established experimental systems to test novel therapeutic strategies. These accomplishments position us to move into the next phase of the projects. Ultimately, our goal is to translate these discoveries into clinical strategies that improve survival and quality of life for patients with lung cancer. The progress achieved in this first year represents an important step toward that goal.