Faisal Aziz is a postdoctoral researcher at the University of Minnesota investigating how environmental stressors impair cancer immunotherapy by identifying an immune regulating phosphatase as a key molecular brake that drives T cell exhaustion. In this Postdoc Portrait interview, he shares how everyday stress plays a role in how well cancer immunotherapy works and how that factor is not considered enough during treatment.
Targeting T Cell Exhaustion and Environmental Stressors
Q | What drew you to cancer immunology?
I was drawn to cancer immunology by a simple observation during my graduate training: two patients with the same tumor type, same stage, same treatment—yet one recovers while the other does not. That difference, I realized, often comes down to the immune system.
But when I started working with tumor-infiltrating lymphocytes, I saw their heartbreaking fragility. These T cells entered the tumor armed to kill, yet within days they shut down. I became obsessed with understanding why.
Then I looked beyond the tumor. I noticed that many of my lab's poorest-responding patients had something in common: heavy alcohol use, chronic stress, or diets loaded with capsaicin-rich foods. Was the immune system being attacked from the outside and the inside?
That question led me to a protein called suppressor of T cell receptor signaling (STS1). I discovered that alcohol metabolites, stress hormones, and even capsaicin all converge on this single phosphatase—accelerating T cell exhaustion. Searching for an inhibitor, I found Rebamipide, a gastric drug that blocks STS1.
What drew me in was the chance to connect real-world lifestyle factors to a molecular mechanism, then repurpose a safe, cheap pill to fight back. That intersection of immunology, environmental exposures, and rapid translation is where I belong.
Q | What scientific problem are you trying to solve?
My work addresses a central paradox in cancer immunotherapy: why T cells, even when powerfully activated, often fail to eliminate solid tumors.
We can engineer a T cell to recognize cancer beautifully. We can infuse billions of them. Yet inside a tumor, these same cells become dysfunctional—a state known as exhaustion. The core problem isn't whether T cells can find cancer, but whether they can sustain their function long enough to finish the job.
But exhaustion doesn't happen in isolation. I study how everyday lifestyle factors accelerate it. Alcohol metabolites directly impair mitochondrial respiration in T cells. Chronic stress elevates glucocorticoids, which suppress T cell receptor signaling. Even capsaicin—the compound that makes chili peppers spicy—can, at high or repeated doses, trigger transient receptor potential vanilloid one(TRPV1)-mediated inflammation that paradoxically shields tumors from immune attack.
So, my research asks: do these environmental stressors push T cells over the edge faster? Using knockdown screens in primary human T cells exposed to alcohol, stress hormones, or capsaicin, I have identified STS1 as a common molecular checkpoint that integrates these signals. My preliminary data show that the drug Rebamipide inhibits STS1 and restores T cell killing—even under stress.
The problem I am solving is how to keep T cells metabolically fit for the long fight against cancer, despite the stressors modern life throws at them.
Converging Stress Signals in T Cell Exhaustion
Q | What’s one thing you learned about T cell exhaustion that you didn’t expect?
I didn't expect that chili peppers, beer, and a bad week at work could all speak the same molecular language to a T cell.
When I started studying T cell exhaustion, I thought the enemy was strictly inside the tumor—hypoxia, low glucose, suppressive cytokines. Then I began testing lifestyle factors almost as an afterthought. To my surprise, ethanol (at blood concentrations reached after two drinks) suppressed T cell signaling within hours. Corticosterone (a stress hormone) did the same. Even capsaicin—at doses found in spicy meal remnants—triggered TRPV1 on T cells, leading to calcium overload and accelerated exhaustion.
But the real shock came when I mapped these signals. All three converged on STS1. Alcohol, stress, and capsaicin each upregulated or activated this single phosphatase. That meant a patient drinking heavily, facing a deadline, and eating spicy food wasn't suffering three separate hits—they were hitting the same molecular brake three times.
Then Rebamipide changed everything. One old pill blocked STS1 and reversed all three insults. What I learned is that environmental factors aren't just background noise. They are active, targetable drivers of immune failure. And sometimes the answer was on a pharmacy shelf the whole time.
Q | If your research succeeds, what could it change for science or society?
If my research succeeds, it could change three things: how we think about lifestyle, how we treat cancer, and how fast science helps patients. First, for society: millions of people consume alcohol, live with chronic stress, or eat capsaicin-rich foods daily. Right now, no one warns cancer patients that their spicy meal or glass of wine might accelerate T cell exhaustion. My work could change that—not with fear, but with precision. If we confirm that these factors converge on STS1, we can give patients simple, evidence-based guidance. Better yet, we can intervene with Rebamipide, a safe, cheap, repurposed pill that blocks STS1 regardless of the trigger. Second, for science: I've shown that alcohol, stress hormones, and capsaicin all hit the same molecular brake on T cells. This suggests that environmental immunology—studying how daily exposures shape immune function—deserves a seat at the cancer immunotherapy table. We should be screening lifestyle factors alongside drug libraries. Ultimately, success means a future where a patient undergoing chimeric antigen receptor (CAR) T cell therapy receives not only cutting-edge cell engineering but also a stomach ulcer pill and a personalized lifestyle plan. Because beating cancer requires understanding not just the tumor, but the life the patient lives every day.
Q | What question are you most excited to answer next?
I'm most excited to answer this question: Does blocking STS1 with Rebamipide protect T cells from the combined assault of alcohol, stress, and capsaicin in living organisms—not just in a dish? Right now, I have compelling data in human T cells cultured with ethanol, corticosterone, and capsaicin. Rebamipide inhibits STS1 and restores killing function. But a culture plate is not a patient. So, my next step is a mouse model of solid tumor where I can control three variables: alcohol intake (voluntary drinking), chronic stress (restraint or predator odor), and dietary capsaicin. I will infuse tumor-specific T cells—with and without Rebamipide—and ask: Do alcohol, stress, and spicy food together accelerate T cell exhaustion faster than any single factor? Does oral Rebamipide reach sufficient levels in T cells to block STS1 in vivo? Does Rebamipide improve tumor control in mice living with these real-world exposures? If yes, I want to move toward a small human trial—patients with cancer that have heavy alcohol use or high stress—adding Rebamipide to their immunotherapy. I'm excited to take environmental immunology from observation to intervention.
Responses have been edited for length and clarity.
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