Glucose levels may affect immunotherapy in lung cancer.A study from Israel presented at ELCC 2026 supports the role of glucose control as a modifiable host factor that could improve the effectiveness of immune checkpoint inhibitors in the treatment of non-small cell lung cancer (NSCLC).
Study participants with balanced glucose levels had significantly better progression-free survival (PFS; median 22.43 vs 17.25 months; p=0.01) and overall survival (OS; median 28.66 vs 23.44 months; p=0.01). The benefit was consistent across histological subtypes and treatments. [ELCC 2026, abstract 163eP]
The PFS benefit was evident among participants with adenocarcinoma (median 22.21 vs 13.5 months; p=0.01) and squamous cell carcinoma (median 26.7 vs 14.4 months; p=0.01). A similar pattern was observed in both subgroups for OS (median 26.6 vs 15.37 months; p=0.01 and 29.3 vs 23.6 months; p=0.01, respectively).
Among participants who had been treated with immunotherapy only, well-controlled glucose was associated with substantially longer PFS (median 25 vs 15 months; p=0.01) and OS (median 43 vs 19 months; p=0.01).
For those who had undergone chemo-immunotherapy, balanced glucose levels were also associated with improved PFS (median 15 vs 11 months, p=0.05), but only a trend for OS (median 22 vs 13 months; p=0.07).
“Host metabolic factors, such as glucose regulation, may influence therapeutic response [in immunotherapy]. Poor glucose control has been associated with impaired immune function, potentially attenuating the therapeutic effects of immune checkpoint inhibitors,” according to the investigators, led by Dr Walid Shalata from the Ben Gurion University of the Negev, Beer Sheva, Israel.
Metabolic alterations have long been recognized as a hallmark of cancer. Evidence suggests that manipulation of glucose metabolism may be beneficial for controlling the growth of cancer cells and helping the immune system elicit an efficient and protective response to cancer cells. [Cancers (Basel) 2020;12:2940]
Targeting glucose metabolism holds promise as an anticancer strategy, given the critical role that metabolic pathways play in regulating both T cell function and cancer cell growth. However, there is insufficient data on metabolic reprogramming in immune cells during their activation. [Cancers (Basel) 2020;12:2940]
To evaluate the impact of glucose levels on the efficacy of immunotherapy in individuals with metastatic NSCLC, the investigators retrospectively evaluated 234 NSCLC patients (median age 66.4 years, 67.5 percent men) who had received immune checkpoint inhibitors, either alone or in combination with chemotherapy.
Seventy percent of the overall population had adenocarcinoma, and the remaining 30 percent had squamous cell carcinoma. Approximately a third (34.62 percent) had unbalanced glucose levels, and nearly half (48.7 percent) were current smokers.
Seventy-seven percent of the participants received chemo-immunotherapy. The most commonly administered immunotherapy was pembrolizumab (80.3 percent); the rest of the participants received ipilimumab plus nivolumab. About 60 percent had lymph-node involvement, 53.4 percent had metastasis in the lungs, approximately 30 percent had bone metastasis, and 18.4 percent had brain metastasis.
“[Taken together, the findings suggest that] the integration of metabolic management into oncologic care could maximize survival outcomes,” the investigators concluded.