Abstract 4284: The effect of resveratrol and curcumin on the expression of immune modulatory molecules on colorectal cancer cells
Authors: Braun Donald P. , Fagla Bani M. , Ali Irshad 
Published: August 2015

Modulation of antitumor immunity in patients by targeting different regulatory molecules on immune cells and tumor cells has been demonstrated in recent clinical studies. To date, the most successful strategy relies on antibodies directed against ligands or receptors that regulate either the development or expression of antitumor immunity. Prominent targets include CTLA4 on Treg cells; programmed cell death ligands 1 and 2 (PDL1/PDL2) on tumor cells; and the programmed death receptor (PD1) on T cells. But chronic infusion of antibodies to modulate these targets in patients is not without concerns related to tolerance, morbidity, and development of resistance. Thus, more tolerable approaches in cancer patients to supplement the efficacy of current modalities should be developed. In the present study, natural products Resveratrol (RV) and Curcumin (C) were tested for effects on expression of co-stimulatory molecule, CD80; regulatory ligands PDL1 and PDL2; and programmed death receptor, PD1 on human colorectal cancer (CRC) cells. CRC cells were obtained from surgical specimens of patients with metastatic disease involving stomach (CRC1), ovary (CRC2), and a primary neoplasm (CRC3). Tissues were disaggregated with collagenase/DNAse to obtain single cell suspensions and cultured to obtain short term cell lines. Each line was treated with RV (5ug/ml) or C (50μM) for 72h, following by RNA extraction and gene expression profiling using customized T-cell and B-cell activation quantitative RT-PCR arrays. The most consistent effect was on expression of CD80 which was increased significantly by both RV and C on all 3 CRC lines. Expression of CD80 was increased 9, 58 and 6-folds by RV and 6, 123 and 27-folds by C in CRC1, CRC2 and CRC3 respectively. There was a differential effect of RV and C on PDL1 and PDL2 in these 3 lines. In CRC1, PDL1 was suppressed 2 and 3-folds and PDL2 was suppressed 7 and 3-folds by RV and C respectively. In CRC2, PDL1 and PDL2 expression was increased 3 and 17-folds by RV whereas C had no significant effect on either ligand. And in CRC3, PDL1 and PDL2 expression was not significantly affected by RV while the only effect of C was a 3 folds increase in PDL2 expression. Expression of PD1 was also not affected consistently by either RV or C. Expression of PD1 was not affected in CRC1 by either RV or C; was increased 7 and 9 folds in CRC2; and was increased 3 and 21-folds by RV and C in CRC3 respectively. These results demonstrate that human colorectal cancer cells express different immunoregulatory molecules that are sensitive to modulation by the natural products, RV and C. The consistent upregulation of CD80 suggests that chronic administration of these well tolerated agents might enhance the immunogenicity of CRC cells in patients. Furthermore, for specific tumors, favorable modulation of both programmed death ligands and receptor is possible.

Citation Format: Donald P. Braun, Bani M. Fagla, Irshad Ali. The effect of resveratrol and curcumin on the expression of immune modulatory molecules on colorectal cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4284. doi:10.1158/1538-7445.AM2015-4284