IT-33USE OF IFN-ALPHA AND POLY-ICLC AS CHEMOKINE MODULATORS FOR IMMUNOTHERAPY IN GLIOMAS

Chemokines are known to play an integral role in the cellular trafficking of the immune system, which has important implications in immunotherapy of cancers. Expression of CXCL10/IP10 and CCL5/RANTES has been shown to correlate with increased infiltration of effector T cells and natural killer (NK) cells; conversely expression of CCL22/MDC has been associated with suppression of the adaptive immune response through recruitment of regulatory T cells. Our study evaluated the effects of polyinosinic polycytidylic acid stabilized with lysine and carboxymethylcellulose (poly-ICLC) and IFN-alpha individually and in combination on the expression of chemokines in glioma tissue samples and in glioma cell lines cocultured with myeloid cells to simulate the tumor microenvironment. We found that IFNα as a single agent produced the greatest increase in the expression of CCL5 and CXCL10 while minimizing the expression of CCL22. The addition of poly-ICLC further increased expression of CCL5 and CXCL10. Patient glioma samples had heterogeneous chemokine expression but demonstrated a similar pattern of expression of chemokines to the coculture and cell lines examined. Our findings support the use of IFN-alpha with poly-ICLC as a potential immunotherapy adjuvant for patients with gliomas.