The immunosuppressive microenvironment of solid tumors poses a daunting challenge to immunotherapy. Researchers led by Ludwig Lausanne’s Denarda Dangaj Laniti and Fernanda Herrera reported in an April publication in Clinical Cancer Research the findings of a phase 1 clinical trial (RACIN) examining whether low-dose radiotherapy (LDRT) can be used to gently turn “cold” (immune-excluded) tumors of various types “hot” in preparation for immune checkpoint blockade (ICB) therapy. The researchers found the LDRT + ICB combination to be manageably safe, with an overall disease control rate of 42%. One ovarian cancer patient even sustained a complete response three years after receiving the combination. Analysis of tumor samples, collected before and ten days after LDRT, revealed that DNA damage response (DDR)-prone tumors that already harbored a few anti-tumor CD8+ T cells showed more anti-tumor T cell activity after LDRT. Those that resisted therapy had, at baseline, a paucity of immunostimulatory myeloid cells and an abundance of suppressive immune cells, such as mucosal-associated invariant T (MAIT) and regulatory natural killer (NK) cells. The study provides rare clinical evidence that low-dose radiation can reprogram immune-excluded metastases and bolster a CD8+ T cell response before immunotherapy is even started, opening a path to potentially expand immunotherapy to cold tumors (see Image gallery). It also identifies biomarkers (like DDR features and immune cell niches) for patient selection in future trials.
Combinatorial delivery of low-dose radiotherapy and immunotherapy to patients with immune-excluded tumors enhances CD8+ T cell functionality
Clinical Cancer Research, 2026 April 17