Radiation therapy overcomes immunotherapy resistance in some cancers

Medical Xpress / Johns Hopkins University School of Medicine / Nature Cancer ^ | July 22, 2025 | Huang, J. et al

[ConservativeMind]

By sparking the immune system into action, radiation therapy makes certain tumors that resist immunotherapy susceptible to the treatment, leading to positive outcomes for patients, according to new research.

In the study, investigators dove deep into the molecular biology of non-small cell lung cancer to pinpoint what happens on a cellular and molecular level over time when the cancer is treated with either radiation therapy followed by immunotherapy or immunotherapy alone.

They found that radiation plus immunotherapy induced a systemic anti-tumor immune response in lung cancers that do not typically respond to immunotherapy. The combination therapy also yielded improved clinical response in patients whose tumors harbor features of immunotherapy resistance.

They collaborated with Willemijn Theelen and Paul Baas at the Netherlands Cancer Institute, who were running a Phase II clinical trial on the effect of radiation therapy followed by immunotherapy, specifically the PD-1 inhibitor pembrolizumab.

With help from Theelen and Baas, Anagnostou's team analyzed 293 blood and tumor samples from 72 patients, obtained at baseline and after three to six weeks of treatment. Patients in the control group received immunotherapy alone, while the experimental group received radiation followed by immunotherapy.

In particular, the team focused on immunologically "cold" tumors—tumors that typically do not respond to immunotherapy. These tumors can be recognized by particular biomarkers: a low mutation burden, no expression of a protein called PD-L1, or the presence of mutations in a signaling pathway called Wnt.

Following radiation and immunotherapy, the team found that "cold" tumors far from the site of radiation experienced a prominent reshaping of the tumor microenvironment. Anagnostou describes this shift as the tumors "warming up," transitioning from little or no immune activity to inflamed sites with strong immune activity, including the expansion of new and pre-existing T cells.

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TOPICS: Health/Medicine
KEYWORDS: cancer; immunotherapy; radiation; treatment

[ConservativeMind]

Radiation can make “cold,” metastasized cancer tumors responsive to immunotherapy.

[ConservativeMind]

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[ComputerGuy]

Had my 6-month chest scan last Tuesday.
The results were good. We keep hanging in there.
I can’t help but feel like somebody’s looking out for me.

[KittyKares]

Happy to hear it. Keep doing whatever you’re doing.

[so_real]

I'm still on the fence about radiation causing more harm than benefit by weakening the host and encouraging metastasis of the disease :

Effects of radiation on the metastatic process
https://molmed.biomedcentral.com/articles/10.1186/s10020-018-0015-8

Conclusion
There is abundant evidence from in vivo and in vitro experiments that ionizing radiation, applied to cancer cells or host cells, to the tumor, the whole host or the putative site of tumor development may stimulate the metastatic process. Clinical observations do not directly confirm these data, leaving open the question whether or not radiotherapy enhances metastasis. The overall net outcome of radiotherapy is beneficial as it may reduce metastasis and prolong survival. This therapeutic benefit does not exclude a limitation of the benefit by negative effects of the irradiation on the cancer cells or on the host. The present review of literature suggests clinical trials to investigate correction of the pro-invasive and pro-metastatic activities of radiation by anti-inflammatory or other agents shown to be effective in preclinical settings.

I have seen personally so much success with the "do no harm but totally un-medically sanctioned" therapies with fenbendazole, artemisinin, and ivermectin that I personally would exhaust those routes before submitting to radiation.

[ConservativeMind]

This is about remote tumors not responding to immunotherapy.

I do agree with you and have posted about how radiation does the effect you described.

[Honorary Serb]

New!

[UB355]

This is how I was treated. Radiation, Chemo, then Keytruda. It did the trick for me.

[bitt]

p