Involvement of the Immune System in Intrinsic Radiosensitivity

Involvement of the Immune System in Intrinsic Radiosensitivity

Radiotherapy is one of the major treatments for cancer. It may be indicated in more than two-thirds of patients, regardless of cancer location or disease stage. The mechanisms of radiotherapy action are numerous: halting tumor proliferation, inducing tumor cell death, triggering anti-tumor immune responses, and ensuring both local and systemic tumor control. As a result, current treatments are highly effective, providing, for instance, a 5-year overall survival rate of about 90%-95% for localized breast and prostate cancers.

In everyday clinical practice, the indications for radiotherapy are based on the benefit-to-risk ratio concerning toxicity. In most cases, radiotherapy causes mild to moderate acute or late side effects, depending on the patient and the volumes irradiated. However, in 1% to 5% of treated patients, these side effects can be severe, unexpected, and often unexplained. The cause of this toxicity remains poorly understood and largely unexplored, especially concerning the intrinsic radiosensitivity of patients.

The PROUST study (French Registry for Review of Morbidity and Mortality; RMM) was initiated in France to prospectively collect clinical, dosimetric, and biological data on individual radiosensitivity in patients who experience severe radiation-induced toxicity. The goal of this study is to better characterize patients with severe radiation-induced toxicities and identify the cellular factors involved in this toxicity.

Although the aim is to identify the cellular and molecular immune factors involved in severe radiation-induced toxicity, we currently cannot determine whether the immune monitoring observed in radiosensitive patients is a consequence of the toxicity itself or of radiotherapy. To answer this question, we have decided to create a control cohort, called TRANSPROUST, which includes patients treated with radiotherapy but who did not experience severe radiation-induced toxicity. After obtaining consent from patients who were treated with radiotherapy but did not develop severe toxicity, we will collect blood samples similar to those taken from the severe toxicity cohort.

These samples will undergo flow cytometry analysis, and the results will be compared with those of patients included in the PROUST cohort.

Inclusion Criteria:

• Age ≥ 18 years
• Patients who have been treated with radiotherapy
• Absence of toxicity grade 2 or higher
• Patients without psychiatric, sociological, family, or geographical difficulties that could interfere with patient compliance to the protocol or follow-up
• Information and signed informed consent
• Affiliated with social security

Exclusion Criteria:

• Inability to obtain patient consent
• Patient refusing blood sample collection
• Patient deprived of liberty or under legal protection (under guardianship, under curatorship)
• Patients who have experienced radiation-induced toxicity of grade 2 or higher
• Disease progression, relapse
• Patient under State Medical Aid