Ishwaree Datta is a postdoctoral researcher at the University of California, Santa Barbara (UC Santa Barbara) studying how solid tumors adapt to survive immune system attacks. In this Postdoc Portrait interview, she shares how cancer cells fight back against host immune system attacks and how she plans to use those stress responses to find vulnerabilities in cancer cells.
Decoding Immune Attacks and Cancer Cell Adaptation
Q | What drew you to cancer and the immune system?
I didn't set out to study cancer. My scientific journey began in a microbiology lab, studying how bacteria acquire iron in a nutrient-deficient environment. I was studying how a simple single-cell organism solved the problem of survival under scarcity. What captivated me wasn't the organism itself, but the question underneath: How does something small and vulnerable persist in a hostile environment? This question has followed me across every system I've worked in. During graduate school, I used fruit flies to study how tumors grow and resist treatment. Now, as a postdoctoral fellow, I work with human cancer cells and immune cells in the context of ovarian cancer. The models have changed, but the question hasn't.
When I first observed trogocytosis—a process in which macrophages repeatedly bite into tumor cells—only to see those cancer cells still survive and keep dividing, I felt the urgency of the question snap into focus. How a cancer cell can withstand an immune attack and live to fight another day is a clinically devastating phenomenon that nobody has fully explained. Understanding this mechanism and finding ways to disrupt it became the center of my scientific research to develop more effective immunotherapies in the future.
Q | What scientific problem are you trying to solve?
Cancer immunotherapy has transformed treatment for many patients, yet most solid tumors eventually find a way to survive. However, we still don't fully understand how cancer cells survive. My research asks a deceptively simple question: What happens to a cancer cell that gets attacked by the immune system but doesn't die? To decipher this, I study the fundamental changes in cancer cells that do not die following macrophage trogocytosis. The surviving cancer cells appear to activate stress-response programs that potentially help them endure future immune attacks, likely driving cancer relapse and treatment resistance. Thus, by understanding how cancer cells persist after immune injury, I hope to identify new vulnerabilities that could be targeted with existing drugs and combinatorial therapies, turning incomplete immune responses into lasting cures.
Overcoming Resistance to Immunotherapy in Solid Tumors
Q | What’s one thing you learned from cancer cell survival that you didn’t expect?
When I began studying immunotherapy targeting solid tumors like breast and ovarian cancer, I expected the immune cells to be the main character in this story. Specifically, when I began studying how macrophages attack tumor cells, I assumed the critical variables would all be on the immune side, that is, how efficiently macrophages engaged, how much cancer cell membrane they removed by trogocytosis, and how many bites it took to trigger cell death.
What I didn't expect was how much the cancer cell had to say about its own fate. Thus, when I looked closely at tumor cells that survived trogocytosis, I found that they weren't passive victims waiting for a killing blow. The attacked cancer cells actively responded by mounting stress responses, rewiring their metabolism, and upregulating survival signals within minutes of being attacked.
This unexpected discovery reframed my entire research map. The question was no longer just, "How do we make macrophages better killers?" but, "How do we stop cancer cells from talking back or evolving to escape from immune attack?" This shift from trying to make more efficient immune cells to identifying the targetable pathways that tumor cells use to evade immunotherapy is what drives my work today.
Q | If your research succeeds, what could it change for science or society?
This work could explain why solid tumors recur after immunotherapy and point toward combination treatments that prevent cancer cells from adapting to immune attack in the first place.
Q | What question are you most excited to answer next?
I want to uncover whether the cancer cells that survive immunotherapy are the same ones that seed relapse; if they are, understanding targetable cancer cell survival mechanisms would be the frontrunner for therapeutic interventions.
Responses have been edited for length and clarity.
Are you a researcher who would like to be featured in the “Postdoc Portraits” series? Send in your application here.
