Usage Information
Citation Information: JCI Insight. 2019;4(7):e126853. https://doi.org/10.1172/jci.insight.126853.
Abstract
Recruitment of myeloid-derived suppressor cells (MDSCs) into tumors induces local immunosuppression in carcinomas. Here, we assessed whether SX-682, an orally bioavailable small-molecule inhibitor of CXCR1 and CXCR2, could block tumor MDSC recruitment and enhance T cell activation and antitumor immunity following multiple forms of immunotherapy. CXCR2+ neutrophilic MDSCs (PMN-MDSCs) were the most abundant myeloid cell subset within oral and lung syngeneic carcinomas. PMN-MDSCs demonstrated greater suppression of tumor-infiltrating lymphocyte killing of targets compared with macrophages. SX-682 significantly inhibited trafficking of PMN-MDSCs without altering CXCR2 ligand expression. Trafficking of CXCR1+ macrophages was unaltered, possibly due to coexpression of CSF1R. Reduced PMN-MDSC tumor infiltration correlated with enhanced accumulation of endogenous or adoptively transferred T cells. Accordingly, tumor growth inhibition or the rate of established tumor rejection following programed death–axis (PD-axis) immune checkpoint blockade or adoptive cell transfer of engineered T cells was enhanced in combination with SX-682. Despite CXCR1/2 expression on tumor cells, SX-682 appeared to have little direct antitumor effect on these carcinoma models. These data suggest that tumor-infiltrating CXCR2+ PMN-MDSCs may prevent optimal responses following both PD-axis immune checkpoint blockade and adoptive T cell transfer therapy. Abrogation of PMN-MDSC trafficking with SX-682 enhances T cell–based immunotherapeutic efficacy and may be of benefit to patients with MDSC-infiltrated cancers.
Authors
Lillian Sun, Paul E. Clavijo, Yvette Robbins, Priya Patel, Jay Friedman, Sarah Greene, Rita Das, Chris Silvin, Carter Van Waes, Lucas A. Horn, Jeffrey Schlom, Claudia Palena, Dean Maeda, John Zebala, Clint T. Allen
Usage data is cumulative from March 2022 through March 2023.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 2,869 | 516 |
| 277 | 141 | |
| Figure | 445 | 5 |
| Supplemental data | 61 | 6 |
| Citation downloads | 54 | 0 |
| Totals | 3,706 | 668 |
| Total Views | 4,374 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
