Cross-Cancer Analysis Reveals a Distinct Pattern of Immune Modulation During Curative Radiation Therapy.

Purpose: Radiation therapy (RT) is a cornerstone of curative cancer treatment, yet its immune effects are not fully understood. This study examined systemic immune profile changes in patients undergoing RT for solid tumors.

Methods and materials: Patients with localized head and neck cancer, non-small cell lung cancer, rectal cancer, or extremity soft tissue sarcoma treated with curative RT (>45 Gy, 1.8-3 Gy/fraction) were enrolled. Baseline and post-RT (after 45 Gy) blood samples were analyzed using multiplex Luminex cytokine assays and high-dimensional mass cytometry (cytometry by time-of-flight). Immune alterations were correlated with patient outcomes.

Results: Thirty-seven patients treated with curative RT for head and neck cancer (n = 8), non-small cell lung cancer (n = 8), rectal cancer (n = 7) or soft tissue sarcoma (n = 14) were enrolled. Approximately 50% of patients received concurrent chemotherapy. At a median follow-up of 21 months, there were 3 local and 12 distant recurrences. Cytokine analysis showed increased C-X-C motif chemokine ligand 12 (P = .044) and monocyte chemoattractant protein-1 (P < .001), both important in monocyte trafficking and mobilization. Consistent with the cytokine changes, cytometry by time-of-flight demonstrated increased monocytes (P < .001) and reduced natural killer and B cells (P < .001). Circulating CD4 effector T cells decreased in patients who developed distant metastases (P = .049) but remained unchanged in recurrence-free patients. These effects were independent of tumor type and chemotherapy, indicating conserved immune changes following RT.

Conclusions: We identified a distinct pattern of immune change across all tumor types analyzed in response to RT, with increases in protumoral myeloid cell populations, reductions in B cells and natural killer cells, and a significant decrease in CD4 effector T cells among patients who developed distant metastases.