Horization: How radiation on the immune system helps kill cancer

In the study, it was published July 22 in Nature CancerResearchers keep deeply in the molecular biology of non -cell lung cancer to determine what is happening at the cellular and molecular level over time when cancer is treated either by radiotherapy followed by immunotherapy or immunotherapy alone. They found that radiation, in addition to immunotherapy, caused an anti -tumor immune response to lung cancers that do not usually respond to immunotherapy. Complex therapy also resulted in an improved clinical response in patients whose tumors are characterized by immunotherapy resistance features.

Clinically, the results indicate that radiotherapy can help overcome immunotherapy in some patients.

“For a small part of lung cancers where we do not expect treatment responses, the radiation may be particularly effective to help the Precision ONCOLOGY Analytics, co -commander of the Johns Hopkins Council for the molecular tumor and co -manager of the Excellence Center for Lung Cancer in Johns Hopkins.

The researchers have long sought to understand the reason that some tumors have increased resistance to immunotherapy – a treatment strategy that benefits from the body’s immune system to fight cancer cells – and how to interfere with this resistance.

Radiotherapy has been suggested as one possible to urge a systematic immune response due to a unique phenomenon called Easter effect. Radiation at the essential tumor site usually leads to the death of cancer cells and the release of their contents in the local macro and the local environment. Sometimes, the immune system discovers these contents, learns the molecular imprint of the tumor, then activates immune cells around the body to attack cancer cells in the tumor sites that were not radiation targets, including some away from the basic cancer in the body.

Because of this effect, radiotherapy can improve the quality of immunotherapy against cancer, even away from the original radiation location. However, only little is known about molecular biology behind the calm effect, or how to predict the date of the illusion of patients.

To study this phenomenon, Anagnostou and his colleagues got samples of patients with lung cancer at different times throughout the treatment journey and from different locations in the body, not only in the main tumor site. They collaborated with Willemijn Thelen and Paul Baas at the Netherland’s Cancer Institute, who were running a clinical trial for the second stage on the effect of radiotherapy followed by immunotherapy, specifically PD-1 PEMBROLIZUMAB.

With the help of Thelen and Baas, the Anagnostou team analyzed 293 samples of blood and tumor from 72 patients, obtained primarily 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.

Then the team conducted multi -samples on samples – that is, combining different “omics” tools, including genome science, transport signs, and various cell tests – to describe what was happening deeply for the immune system systematically and in the local accurate environment in tumor sites that were not exposed directly to radiation.

In particular, the team focused on the immune “cold” tumors – tumors that do not usually respond to immunotherapy. These tumors can be recognized by certain vital indicators: a low mutation burden, there is no expression of a protein called PD-L1, or the presence of mutations in the signal path called Wnt.

After radiation and immunotherapy, the team found that “cold” tumors are far from the radiation site that saw a prominent reshaping of the microscopic environment of the tumor. Anagnostou describes this shift as “warm -up” tumors, which are transmitted from a small or non -immune activity to inflamed sites with strong immune activity, including the expansion of new and pre -present T cells.

“Our results arise how radiation can enhance the anti -tumor immune response in lung cancer is unlikely to respond to immunotherapy alone,” says study author Lead Study Justin Huang, who led multi -analyzes. “Our work emphasizes the value of multidisciplinary international cooperation in translating the visions of cancer biology to clinical importance.” Huang was awarded the Paul Erlich Award for Research for the year 2025 in recognition of the leading discoveries by young investigators and teachers of faculty members at the University of Johns Hopkins University.

With Kellie Smith, PhD, Associate Professor of Oncology at the Johns Hopkins Kimmel Cancer and Bloomberg Institute ~ Kimmel Immunotherapy Cancer, Anagnostou team focused on patients who were focusing on patients in the long term. In cell cultures, they emphasized that the T cells that expand in patients who received radiation and immunotherapy already recognizes the new mutation associated with patient tumors.

Finally, by tracking the results of patients from the clinical experiment, the team noted that patients with cold immune tumors “heat” due to radiotherapy had better results than those who did not receive radiotherapy.

Anagnostou says: “It was very exciting, and made everything really would come a complete circle,” says Anagnostou. “We not only picked up the calm effect, but we linked the immune response to clinical results in the tumors where one does not expect to see immunodeficiency responses.”

Using samples of the same groups of patients, the team recently worked to capture the body’s response to immune therapy by detecting the DNA of the tumor (CTDNA) in the blood. This work was presented on April 28 at the annual meeting of the American Cancer Research Association in Chicago.

The additional authors include in this study Belcaid, Mimi Najjar, Mimi Najjar, Dapne Van der Geest, Dipika Singh, Christopher Cherry, Archana Ballan, James R. White, James R. White, James R. Michel M. Van Den Hevel from the Center of Radbod University.

The study was supported by the Johns Hopkins Bloomberg ~ Kimmel Immunomodus and National Health Institutes (Grant #Ca121113).

Anagnostou receives funding for the University of Johns Hopkins from Astrazeneca, Labcorp/Personal Genome Diagnostics, Defi Diagnostics, and Bristol Myers Squibb in the past five years. She is a consultant member of the Board of Directors (compensation) for Astrazneca and Nickel scientists, and she got Honorara from basic medicine and Guardant and Labcorp/Personal Genome. It is an inventor in six patent requests submitted by Johns Hopkins University, which relates to genetic analyzes of cancer, monitoring of CTDNA therapeutic response and immune features to respond to immunosuppressive therapy for one or more. Under the conditions of these licensing agreements, the university and inventors have the right to obtain fees and distributions of kings. The conditions of these arrangements are managed by the University of Johns Hopkins according to its opposition policies.