Memorial Sloan Kettering Cancer Center (MSK) released its March 2, 2026 research highlights, pointing to new findings in cancer metabolism, microplastic-related immune disruption, immune cell regulation tied to immunotherapy, and a phase 3 kidney cancer trial. The updates span lab studies and clinical research, with several results framed as potential paths to more targeted treatments and better patient selection for immunotherapy.
One of the featured studies focuses on a lesser-known role of the tricarboxylic acid (TCA) cycle, which is usually described as a core energy-producing pathway in cells. MSK reports the work suggests the TCA cycle also performs a kind of mitochondrial “waste-management” by helping clear excess citrate, an early product of the cycle that can accumulate when cells make more than they can use or remove.
TCA cycle study spotlights citrate “clearance”
In MSK’s summary, citrate buildup inside mitochondria can trigger a stress response that slows protein production and cell growth. The research, from the lab of MSK Sloan Kettering Institute cell biologist Lydia Finley and led by Abigail Xie and Julia Brunner, indicates that metabolite clearance is an essential function of the TCA cycle alongside energy generation and biosynthesis support.
Because many cancer cells require high and tightly managed metabolism to sustain growth, MSK says the study suggests some tumors may rely on parts of the TCA cycle not only for energy, but also to prevent citrate from accumulating. MSK adds that this dependence could represent a vulnerability: forcing citrate to build up could trigger the stress response and slow tumor growth, which the researchers describe as a possible therapeutic opportunity.
Microplastics tied to impaired immune “housekeeping”
Another highlighted line of research examines what happens when microplastics build up inside immune cells that normally help clean up tissues. MSK reports that an MSK-led team studied polystyrene microplastics taken up by phagocytes—immune cells that engulf harmful materials—and found the exposure made these cells less effective at clearing dead and dying cells through efferocytosis.
In the MSK summary, the same microplastic exposure also reduced phagocytes’ ability to remove infectious agents including bacteria and fungi, and the researchers noted that disrupting these “housekeeping” functions could contribute to broader health problems. The work was led by Ana Codo, a Weill Cornell Medicine graduate student, in the lab of senior author Justin Perry at the Sloan Kettering Institute.
A related publication record describes a mechanism centered on methylglyoxal (MGO), a reactive metabolic byproduct. In that report’s abstract, the authors state that polystyrene microplastic accumulation disrupted efferocytosis by impairing apoptotic cell digestion in multiple types of macrophages and in Sertoli cells (specialized testes phagocytes) in vitro, and that exposure also suppressed efferocytosis and caused damage in the lungs, liver, and testes in vivo.
The same abstract describes dysregulated metabolic and phagolysosome processes in microplastic-loaded, efferocytotic macrophages, including MGO accumulation and increased MGO glycation of glucose-6-phosphate dehydrogenase, which it calls an enzyme required for apoptotic cell digestion. It also reports that overexpression of the MGO-detoxifying enzyme glyoxalase-1 rescued microplastic-induced defects in apoptotic cell digestion in vitro and in vivo.
MSK’s write-up similarly emphasizes that microplastics caused MGO to accumulate inside phagocytes, interfering with metabolism and suppressing efferocytosis, and it says boosting the ability to remove MGO by increasing glyoxalase-1 reversed the effect. Dr. Perry is quoted in MSK’s summary saying, “Because the damage we’re seeing is tied to methylglyoxal, a key metabolite that forms advanced glycation end products, it raises a broader concern: microplastic exposure may connect to processes that lead to the development of diseases of aging and cancer — a link we are continuing to investigate.”
TOX findings and a kidney cancer trial update
MSK also highlighted research into TOX, a protein whose expression is associated with exhaustion of cancer-fighting CD8+ T cells and poorer response to immunotherapy, while its role in CD4+ helper T cells had been unclear. MSK reports a study from immunologist Andrea Schietinger’s lab found TOX plays a different, positive role in CD4+ T cells, and the work was led by first author Brianna Naizir.
In MSK’s description, the researchers discovered TOX is critical for CD4+ helper T cells to produce tumor-fighting molecules including interferon-gamma. However, MSK also says the team found TOX-expressing CD4+ T cells can drive damaging autoimmune reactions in studies of autoimmune vasculitis and type 1 diabetes.
MSK says these findings suggest TOX levels in CD4+ T cells could serve as a marker to help doctors predict which cancer patients will respond best to immunotherapy, and it frames the work as a step toward more precise immunotherapy approaches that account for TOX’s differing functions across T cell types.
On the clinical side, MSK reports results from an international phase 3 trial in advanced clear cell renal cell carcinoma (ccRCC), which it describes as the most common type of kidney cancer. MSK states that about 20% of patients have cancer that has already spread outside the kidney by the time it is found, and that about one-third of patients who have surgery later develop spread.
MSK notes that checkpoint inhibitors are standard first-line drug treatment for patients with advanced ccRCC, but for patients who do not respond or who stop responding, it says there have been no clear next steps. The trial, led by MSK genitourinary medical oncologist Robert Motzer, compared belzutifan (Welireg) plus lenvatinib (Lenvima) against cabozantinib (Cabometyx), which MSK calls a commonly used treatment.
MSK reports the study included 741 patients and found the combination was more effective and longer lasting by its reported measures: 47.2% of patients in the combination group had tumors shrink substantially versus 39.1% in the control group, and after two years 49.5% were still responding versus 25.5% in the control group. MSK adds there were no unexpected side effects in either group, and it says it was too early to determine whether overall survival improved because follow-up is ongoing. MSK says Dr. Motzer presented the results at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium on February 28, 2026.
