Moffitt Study Links Tumor-Immune Types to Lung Cancer Therapy

Findings may help guide more precise immunotherapy decisions for lung cancer patients.

Mar. 5, 2026 at 5:32am

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Researchers at Moffitt Cancer Center have identified distinct spatial tumor–immune ecosystems that predict whether patients with advanced non–small cell lung cancer will benefit from immunotherapy. The findings show that analyzing how tumor and immune cells are organized and interact within the tumor microenvironment may predict disease progression more accurately than PD-L1 status alone.

Why it matters

The results support expanding lung cancer diagnostics beyond single-marker testing toward spatial biomarkers that may help guide more precise immunotherapy decisions. Patients with immune-permissive ecosystems may benefit from checkpoint inhibitors alone, while those with suppressive ecosystems could be directed toward combination therapies or clinical trials earlier.

The details

Using multiplex imaging, spatial statistics and machine learning, investigators analyzed paired pre- and on-treatment biopsies from patients enrolled in a clinical trial combining the HDAC inhibitor vorinostat with the PD-1 inhibitor pembrolizumab. Tumors from patients whose disease progressed were characterized by an immune-suppressive architecture before treatment began, including greater spatial clustering of FoxP3-positive regulatory T cells and PD-1–expressing immune cells near tumor cells. In contrast, tumors from patients with stable disease showed stronger colocalization of CD3- and CD8-positive effector T cells interacting with tumor cells.

  • The findings were published in Cancer Research on March 4, 2026.

The players

Moffitt Cancer Center

A National Cancer Institute-designated Comprehensive Cancer Center located in Tampa, Florida.

Sandhya Prabhakaran, Ph.D.

Co-author and applied research scientist at Moffitt Cancer Center.

Alexander Anderson, Ph.D.

Chair of the Integrated Mathematical Oncology Department at Moffitt Cancer Center.

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What they’re saying

“The primary goal was to define and quantify distinct tumor–immune ecologies in non–small cell lung cancer and determine whether these spatial patterns can predict disease progression and response to immunotherapy.”

— Sandhya Prabhakaran, Ph.D., Co-author and applied research scientist

“It means treating the tumor microenvironment as a dynamic community of interacting cell types rather than isolated tumor or immune cells. Treatment response depends on how these cells are spatially organized and functionally interacting, not just whether specific markers are present.”

— Alexander Anderson, Ph.D., Chair, Integrated Mathematical Oncology Department

What’s next

The findings support moving beyond single-marker testing toward ecosystem-based patient stratification. With further validation and streamlined computational tools, spatial immune profiling could become part of lung cancer diagnostics in the coming years.

The takeaway

This study highlights the importance of analyzing the spatial organization and interactions of tumor and immune cells within the tumor microenvironment to better predict response to immunotherapy for lung cancer patients, moving beyond reliance on single biomarkers like PD-L1.