B. Id Said1, G. Boukhaled2, B. H. Lok3, J. Lukovic1, A. Mesci1, J. N. Waldron1, P. Wong4, B. X. Wang2, D. G. Brooks2, and M. Milosevic1; 1Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada, 2Department of Immunology, University of Toronto, Toronto, ON, Canada, 3Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, 4Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Purpose/Objective(s): Radiation therapy (RT) is a cornerstone in the curative treatment of solid tumors, yet its complex effects on the immune system are not fully understood. The prospective SCIPER study aimed to examine these effects by analyzing changes in the immune profiles of patients undergoing RT for various solid cancers. Materials/
Methods: Patients with a new diagnosis of head and neck cancer (HNC), non-small cell lung cancer (NSCLC), rectal cancer, or extremity soft tissue sarcoma (STS) treated with curative intent RT (>45 Gy, 1.8-3 Gy per fraction) were enrolled. Baseline and post-RT (after 45 Gy) blood samples were collected for multiplex Luminex cytokine analysis and high-dimensional CyTOF of immune cell populations. Immune alterations during treatment were identified and correlated with patient outcomes. Results: Overall, 37 patients treated with curative RT for HNC (n=8), NSCLC (n=8), rectal cancer (n=7) and STS (n=14) were enrolled. Approximately 50% of patients received concurrent chemotherapy. With a median follow-up of 16.5 months, there were no local recurrences and nine distant recurrences. Cytokine analysis (available in only 17 patients) demonstrated significant increases in GCSF (p=0.025) and MCP-1 (p=0.029) during treatment, both important in the mobilization and trafficking of monocytes and other myeloid-derived cell populations. Conversely, there was a significant reduction in IL-12B (p=0.004), an effector cytokine important for CD8 T cell priming, effector cell differentiation and anti-tumor activity. Consistent with the increases in GCSF and MCP-1, CyTOF data (37 patients) demonstrated a significant increase in monocyte populations (p < 0.001) and a reduction in NK cells (p < 0.001) during treatment. Intriguingly, the abundance of circulating CD4 and CD8 T effector cells decreased in patients that subsequently developed distant metastases (p=0.055 and p=0.027 respectively), whereas no significant difference was observed for patients who remained recurrence-free. These observations were independent of tumor type and receipt of chemotherapy, suggesting conserved responses to therapy with tumor outcome and metastasis. Conclusion: This early analysis of the SCIPER study identified a distinct pattern of immune modulation during RT across all tumor types, with increases in pro-tumoral myeloid cell populations and a reduction in effector T cells and NK cells. These findings are consistent with evolution towards an immune suppressed phenotype, which may be associated with a higher risk of distant recurrence. Further analysis and longer patient follow-up will improve our understanding of the relationships between immunoregulatory cytokines, specific cell populations and patient outcome.
