The outcomes and response to treatment with immune checkpoint inhibitors is linked to the health of the thymus – a key part of the body’s immune system.
This is the conclusion from results from a ground-breaking international study presented at the European Society of Medical Oncology (ESMO) Congress, being held October 17-21, 2025, in Berlin, Germany. [1]
“Immune checkpoint inhibitors have transformed cancer treatment, but responses remain limited in some patients,” said lead author Simon Bernatz, MD, a radiology resident and a research fellow at AI in Medicine Program at Mass General Brigham, Boston, USA. as well as a visiting scholar at Harvard Medical School.*
Bernatz noted that current biomarkers for immunotherapy, such as PD-L1 or tumor mutational burden (TMB), focus on tumor characteristics but largely overlook patients’ immune capacity.
Response to immunotherapy
The new study investigated whether thymic health might be associated with response to immunotherapy by analyzing routine chest CT scans from nearly 3500 real-world patients treated with immune checkpoint inhibitors. Using an AI tool based on a deep learning framework developed to carry out multi-layered analysis of data from CT scans, researchers assessed thymic size, shape and structure to score thymic health, and examined how these scores related to patients’ outcomes with immunotherapy.
Results showed that higher thymic health was associated with a 35% lower risk of cancer progression (hazard ratio [HR] 0.65; 95% confidence interval [CI] 0.54-0.77) and 44% lower risk of death (HR 0.56; 95% CI 0.46-0.68) in the group of just over 1200 patients with non-small cell lung cancer included in the study.
There was also a positive association between thymic health and immunotherapy outcomes in patients with other cancers, including melanoma, renal and breast cancers.
Unleashing T-cells
A further part of the study confirmed that the deep learning analysis of CT scans provided a valid proxy for thymic health. The researchers sequenced T-cell receptors and their associated proteins in a sub-group of 464 patients with non-small cell lung cancer (NSCLC). This gave detailed information on T-cell differentiation and function; the results correlated with thymic health as assessed using the new AI tool for analyzing CT scans.
“Immunotherapy relies on unleashing T-cells and the thymus is where T-cells are matured. Our study shows that thymic health is associated with improved immunotherapy outcomes across diverse cancer types,” Bernatz explained.
A missing pillar
Looking to the future, Bernatz believes that these findings suggest that thymic health could serve as a non-invasive biomarker of adaptive immune competence in a range of different cancers.
“Thymic health has the potential to enhance patient stratification in precision oncology,” he said.
“Randomized clinical trials will be needed to establish this in clinical practice. But we think thymic health is one of the missing pillars from current cancer biomarker panels and can start bringing the patient’s immune system into clinical decision making alongside established tumor-centered biomarkers.”
“The main limitation of the finding is that it has not been validated prospectively. We need a prospective study including evaluation of thymic health in patients undergoing immunotherapy,” said Alessandra Curioni-Fontecedro, MD, Ph.D., Director of Oncology at Hôpital cantonal – Service d’oncologie and professor of oncology at the University of Fribourg, Switzerland, who was not involved in the study.
However, Curioni-Fontecedro noted that the inclusion of a validation cohort added to the study’s quality and that, although thymic health is not routinely assessed, chest CT scans are commonly performed in patients with cancer.
“There are many reasons why we need new biomarkers for immunotherapy in cancer patients,” Curioni-Fontecedro noted.
“In lung cancer, we need biomarkers to guide whether to give patients immunotherapy alone or in combination with other treatments, such as chemotherapy. And we need better biomarkers for prognosis in individual patients,” she concluded.
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Note: * Bernatz is currently enrolled in the Ph.D program at Maastricht University, the Netherlands, at the Faculty of Health, Medicine and Life Sciences (FHML). His research interests are in the translational intersection of medical care, radiology, and data science with a focus on bridging the AI translational gap.
Reference
[1] Abstract 108O – “Thymic health is associated with immunotherapy outcomes in patients with cancer ‘, presented by Dr Simon Bernatz during Proffered Paper session 1: Basic science & Translational research on Saturday, October 18, 2025 from 10:15 to 11:45 (CEST) in Hall 5.2 (Nuremberg Auditorium)
Featured image: ESMO 2025; Berlin Germany. Photo courtesy © 2025 European Society of Medical Oncology (ESMO). Used with permission.
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