Heterogeneity of IFN-Mediated Responses and Tumor Immunogenicity in Patients with Cervical Cancer Receiving Concurrent Chemoradiotherapy.

PURPOSE

To ask whether the expression of immune markers and IFN signaling in tumor biopsies changes during concurrent chemoradiotherapy (CCRT).

EXPERIMENTAL DESIGN

Tumor biopsies and peripheral mononuclear blood cells (PMBC) before and immediately after 20 Gy/10 fractions (F) of radiation treatment (RT) from 30 patients with cervical cancer receiving CCRT were evaluated by IHC and qRT-PCR for immune markers and correlated with the short-term response.

RESULTS

Tumor immune response to radiation before and after 10F RT as reflected by CD8 T-cell infiltration had substantial heterogeneity with increases, decreases, and no change all evident. Increases in CD8 T cells during CCRT correlated with the presence of nuclear IRF1 in tumor cells ( = 0.68, < 0.0001) and the patient short-term response ( < 0.01). Similarly, in a subset of patients (∼40%) PD-L1 positivity in tumor cells increased, which also correlated with nuclear IRF1 staining ( = 0.48, < 0.01). Patients with augmented PMBC IFN signature expression after 10F had a significantly higher probability of PD-L1 induction (83% vs. 7%, < 0.0001). Most patients exhibited abundant expression of SERPINB9 and CD47 in tumor cells, and tumor infiltration by CD68 cells. SERPINB9 expression correlated with STAT1 signaling in tumor cells.

CONCLUSIONS

CCRT leads to differential tumor immunogenicity and IFN signaling in patients with cervical cancer, suggesting radiation induction of immunity is limited to a subset of patients and may reflect the heterogeneity of intratumoral induction of IFNs..