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Fabio Ynoe de Moraes: Radiotherapy Can “Heat Up” Cold Lung Tumors and Boost Immunotherapy Responses

Fabio Ynoe de Moraes/scri.queensu.ca

Aug 5, 2025, 15:57

Fabio Ynoe de Moraes: Radiotherapy Can “Heat Up” Cold Lung Tumors and Boost Immunotherapy Responses

Fabio Ynoe de Moraes, Associate Professor at Queen’s University, shared a post on LinkedIn about recent paper by Justin Huang et al., published in Nature Cancer.

“New research shows radiotherapy can ‘heat up’ cold lung tumors and boost immunotherapy responses.

A Nature Cancer phase 2 trial (PEMBRO‑RT) reveals that adding stereotactic body radiotherapy (SBRT) to pembrolizumab can induce systemic immune activation in metastatic non–small cell lung cancer — even in immunologically cold tumors (low TMB, PDL1‑null, or Wnt‑mutated).

Immune boost beyond the radiation field: SBRT triggered abscopal effects — activating interferon pathways, antigen presentation, and both T‑ and B‑cell responses in non‑irradiated lesions.
Clonal expansion of T cells: Combination therapy reshaped the T‑cell receptor repertoire in tumor and blood, expanding both pre‑existing and new clones.
Clinical impact in resistant disease: Patients with cold tumors achieved longer progression‑free survival and tumor shrinkage at distant sites, suggesting SBRT can overcome primary resistance to immune checkpoint inhibitors.
Cold‑to‑hot conversion: Multi‑omic analyses confirmed broad immune gene upregulation, TLS signatures, and tumor microenvironment ‘inflaming’ post‑SBRT.

‘Take‑home’: Radioimmunotherapy may create a therapeutic window to re‑sensitize resistant NSCLC to immunotherapy — moving us closer to personalized combinations that break through ICI resistance.”

Title: Combination of pembrolizumab and radiotherapy induces systemic antitumor immune responses in immunologically cold non-small cell lung cancer

Authors: Justin Huang, Willemijn S. M. E. Theelen, Zineb Belcaid, Mimi Najjar, Daphne van der Geest, Dipika Singh, Christopher Cherry, Archana Balan, James R. White, Jaime Wehr, Rachel Karchin, Noushin Niknafs, Michel M. van den Heuvel, Victor E. Velculescu, Kellie N. Smith, Paul Baas, Valsamo Anagnostou

Read The Full Article at Nature Cancer.

Fabio Ynoe de Moraes: Radiotherapy Can "Heat Up" Cold Lung Tumors and Boost Immunotherapy Responses

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Archana Balan Christopher Cherry Daphne van der Geest Dipika Singh Fabio Ynoe de Moraes immunotherapy Jaime Wehr James R. White Justin Huang Kellie N Smith Michel M. van den Heuvel Mimi Najjar Noushin Niknafs NSCLC Paul Baas Rachel Karchin T cells Valsamo Anagnostou Victor E. Velculescu Willemijn S. M. E. Theelen Zineb Belcaid

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