513 CD26 enzymatic activity modulates efficient migration of adoptively transferred T cells to solid tumors. (9th November 2020)

• Record Type: Journal Article
• Authors: Wyatt, Megan; Bailey, Stefanie; Nelson, Michelle; Knochelmann, Hannah; Smith, Aubrey; RIvera, Guillermo Rangel; Reyes, Amalia Rivera; Paulos, Chrystal
• Is Part Of: Journal for immunotherapy of cancer. Volume 8(2020)Supplement 3
• Page Start: A549
• Page End: A549
• Publication Date: 2020-11-09
• Subjects: Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1136/jitc-2020-SITC2020.0513
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : Background: The inadequate ability of adoptively transferred T cells to eradicate solid tumors limits their use in treatments for patients afflicted with those cancers. Efforts to improve ACT for solid tumors aim to identify strategies that poise T cells for optimal response. We have previously identified a specific subset of CD4 T cells which express high levels of the ubiquitous ectoenzyme dipeptidyl peptidase-4 (DPP-4), also known as CD26, that produce a tremendous antitumor response in solid tumor models. We therefore sought to investigate the importance of CD26 on T cells destined for ACT. Methods: We adoptively transferred tumor specific CD26 + T cells into melanoma tumor-bearing CD26 -/- mice, and continuously blocked the CD26 enzymatic activity of the donor cells in vivo with sitagliptin, an established competitive inhibitor of CD26. Results: Tumors in sitagliptin-treated mice eventually reached study endpoint, while tumors untreated mice were regressed for 130+ days. Tumor infiltration of donor cells and host CD8 and CD4 cells was diminished with sitagliptin treatment. A 32-plex cytokine array of blood plasma revealed a diminished profile of cytokines and chemokines, indicating that the inflammatory response of the T cells was dampened with sitagliptin treatment. Further experiments characterized the ability of CD26 + T cells to respond to tumor trafficking signals with a transwell migration assay and found that sitagliptin treatment significantly impaired their migratory capacity. However, sitagliptin did not impair the ability of T cells to functionally respond to antigen. Conclusions: These data suggest that the enzymatic activity of CD26 is important for the ability of T cells to migrate to the tumor site in order to mount an effective antitumor response. Further investigations into the mechanism behind the role of CD26 are ongoing. Ethics Approval: This study was approved by the Medical University of South Carolina's IACUC, protocol #00488