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Baseline corticosteroid use was associated with worse outcomes and diminished biomarker reliability in patients with non–small cell lung cancer (NSCLC) treated with immunotherapy, according to a study published July 7 in Cancer Research Communications. The study was led by Fumito Ito, M.D., Ph.D., an oncologist and researcher at the University of Southern California.

NSCLC is the most common type of lung cancer, about 87% of all lung cancers, according to the American Cancer Society. The five-year survival rate for non–small cell lung cancer was about 32% for patients between 2015 and 2021.

Non–small cell lung cancer is often treated with immune checkpoint inhibitors (ICIs). These immunotherapies help patients live longer by boosting the immune response against cancer cells to help shrink tumors or slow their growth. Examples include anti–PD-1 drugs such as Keytruda (pembrolizumab) and Opdivo (nivolumab) and anti–PD-L1s such as Imfinzi (durvalumab) and Tecentriq (atezolizumab).

However, corticosteroids are frequently prescribed to manage lung cancer symptoms. Although steroid use for immune-related adverse events does not appear to compromise ICI efficacy, baseline steroid use — that is, prior to or at the start of treatment — has been linked to poorer outcomes, raising concerns about immunosuppressive effects.

The new study evaluated 277 patients treated with immune checkpoint inhibitors at Roswell Park Comprehensive Cancer Center or the University of Southern California. Just 8% were taking steroids at treatment initiation, but these patients experienced significantly lower response rates and shorter progression-free and overall survival. Multivariate analyses identified baseline steroid use as the strongest independent predictor of disease progression and mortality.

Patients who discontinued steroids before immune checkpoint inhibitor therapy had better outcomes than those who continued. “The mere use of steroids was a more influential prognostic factor than the presence of brain metastases,” the authors wrote in their paper. Moreover, the analysis revealed that higher doses of baseline steroids were associated with worse patient outcomes than lower doses.

Baseline steroid use also seemed to affect the usefulness of blood-based immune markers. For instance, patients taking steroids had lower levels of CX3CR1+ CD8+ T cells, which help signal how well the immune system is fighting the cancer.

To explore underlying mechanisms, the researchers also conducted a study using anti–PD-L1 therapy in tumor-bearing mice with and without steroid exposure. In mouse models, steroids blunted the therapeutic benefit of anti–PD-L1 therapy and limited T-cell development. Even when steroids were stopped before treatment, earlier use still appeared to make this marker less reliable.

Similarly, while a neutrophil-to-lymphocyte ratio (NLR) below 5 was associated with better prognosis overall, this relationship was not observed in patients taking steroids, further complicating interpretation of immune biomarkers.

Although the number of patients taking steroids was small and biomarker data were incomplete for some participants, the authors noted these limitations and emphasized that the findings still support efforts to reduce steroid use before starting immune checkpoint inhibitor treatment. They suggested that future studies should explore whether lowering or stopping steroids could lead to better clinical outcomes for patients.

In newly published research on age-related inflammation in ring-tailed and sifaka lemurs, Guevara discovered that perhaps we should rethink the inevitability of inflammaging in humans.

Although similar in many ways, ring-tailed and sifaka lemurs show differences in life pacing and lifespan, making useful comparisons. Because lemurs and humans are primates and share a common ancestor that lived millions of years ago, they offer valuable insights into human evolution.

Her findings, she said, were “surprising.”

“Contrary to our predictions, neither species showed age-related change in either marker of oxidative stress. Neither lemur species exhibited age-related change in inflammation; if anything, contrary to our prediction, ring-tailed lemurs showed marginal declines in inflammation with age,” Guevara said.

This finding, consistent with a few recent studies of other non-human primates, suggests that lemurs avoid the phenomenon of “inflammaging” widely observed in humans.

The study shows inflammaging is not a universal feature of primates, pointing to some differences that might suggest it turns out it’s not even a universal feature of humans, according to Christine Drea, a professor of evolutionary anthropology who was one of the researchers working with Guevara.

What is Inflammaging?

As we grow older, low-grade chronic inflammation sets in, which in turn can cause health problems such as heart disease, strokes, diabetes, cancer and osteoarthritis.

Why inflammaging increases with age in humans, what causes it and how it can be prevented are answers to questions that can unlock critical information to help humans live longer and healthier lives.

Collecting Data from Lemurs

Drea said the team first had to find a way to measure oxidative stress, which can be found in blood, urine and saliva. They settled on urine.

“Our role at the beginning was planning, designing, brainstorming, comparing and getting these samples,” said Drea, who has worked with the Duke Lemur Center since 1999. The Lemur Center does not allow research that will harm the animals.

The next step says Guevara is to conduct similar research with lemurs in the wild.

“There are a lot of good reasons to think that aging can be quite different in captivity and in the wild, and that in itself, is informative to evaluating the degree to which human inflammation is intrinsic versus environmental,” she said.

In the meantime, Guevara says this study serves as the first step in unraveling the question of why humans are suffering from inflammatory-related and age-related conditions and finding ways to treat them.

With a rapidly aging global population, “these insights are essential for mitigating disability and improving quality of life in later years,” she said.