The Yaddanapudi lab investigates the mechanisms by which tumors suppress the immune system and develops novel immune-based cancer treatments, including stem cell-based anti-cancer vaccine and cellular therapies. Research in this lab integrates insights from clinical specimen analyses with mechanistic studies in mouse models to uncover the diverse immune suppressive pathways that inhibit anti-cancer immunity and contribute to immunotherapeutic resistance in patients.

A major focus of studies are on understanding how the tumor microenvironment regulates immune responses, with particular emphasis on cancer-driven disruption of normal myeloid cell development. Cellular and molecular mechanisms by which two key myeloid populations — myeloid-derived suppressor cells (MDSCs) and tumor-associated neutrophils (TANs) — induce T-cell suppression and tolerance are investigated. These cells accumulate in both tumor-bearing animals and late-stage cancer patients, significantly impacting treatment outcomes. The current research aims to characterize how MDSCs and TANs compromise the effectiveness of cancer immunotherapy and to develop targeted strategies to overcome this immune suppression, ultimately improving cancer patient responses to treatment.

The lab also explores why patients may be resistant or develop resistance to tumor-infiltrating lymphocyte (TIL) therapy, a form of cellular immunotherapy, with the goal of engineering these cells for improved effectiveness in next-generation treatments.