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.
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