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

Abstract

<div>AbstractPurpose:<p>To ask whether the expression of immune markers and IFN signaling in tumor biopsies changes during concurrent chemoradiotherapy (CCRT).</p>Experimental Design:<p>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.</p>Results:<p>Tumor immune response to radiation before and after 10F RT as reflected by CD8<sup>+</sup> T-cell infiltration had substantial heterogeneity with increases, decreases, and no change all evident. Increases in CD8<sup>+</sup> T cells during CCRT correlated with the presence of nuclear IRF1 in tumor cells (<i>r</i> = 0.68, <i>P</i> < 0.0001) and the patient short-term response (<i>P</i> < 0.01). Similarly, in a subset of patients (∼40%) PD-L1 positivity in tumor cells increased, which also correlated with nuclear IRF1 staining (<i>r</i> = 0.48, <i>P</i> < 0.01). Patients with augmented PMBC IFN signature expression after 10F had a significantly higher probability of PD-L1 induction (83% vs. 7%, <i>P</i> < 0.0001). Most patients exhibited abundant expression of SERPINB9 and CD47 in tumor cells, and tumor infiltration by CD68<sup>+</sup> cells. SERPINB9 expression correlated with STAT1 signaling in tumor cells.</p>Conclusions:<p>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.</p><p><i>See related commentary by Mondini and Deutsch, p. 3815</i></p></div>