Abstract 271: Monitoring of CCR2 and CCR5 expression on circulating myeloid derived suppressor cells (MDSCs) in non-small cell lung cancer as a correlate of minimum residual disease
Authors: Khan Hamza , Awan Anas , Shishikura Maria , Blevins Carley , Rodgers Kristen , Mei Yuping , Nizam Wasay , Ishiyama Shun , Chen Yun , Battafarano Richard , Bush Errol , Broderick Stephen , Yang Stephen , Orita Hajime , Huang Peng , Tam Ada , Ha Jinny , Housseau Franck , Brock Malcolm 
Published: June 2022

Abstract
Objectives: Myeloid derived suppressor cells (MDSCs) are immature cells that aid in cancer progression and dissemination via immune system suppression. Previous work has shown that CCR 2 (C-C chemokine receptor) and CCR 5 expression on MDSCs is increased in non-small cell lung cancer (NSCLC). We hypothesized that patients with lung cancer will have detectable peripheral MDSCs with CCR2 and CCR5 expression preoperatively, that it would decrease immediately postoperatively, and then increase longitudinally if tumor recurs.
Materials & Methods: As part of a prospective longitudinal study, whole blood samples were obtained from patients suspected to have primary lung cancer prior to surgery. Patients were excluded if they were minors, could not provider consent, had malignancy within the past 10 years or any immunosuppressive condition. Blood samples were obtained prior to surgery or at follow-up in clinic and processed within 1 hour of acquisition. We stained samples via 2 different methods: 1) whole blood and 2) peripheral blood mononuclear cells (PBMC) extracted from Ficoll density gradient and determined that whole blood staining had superior results. Samples were analyzed via flow cytometer and gated after defining MO (monocytic)-MDSCs as CD33+HLADRlow/-CD14+ and PMN-MDSCs as CD33+HLADR-CD15+. MDSCs were reported as a percentage of live leukocytes and means were reported with T-test performed for statistical analysis.
Results: A total of 18 patients were recruited with a median age of 69 years (63.8-75) and 61% (11/18) females. Adenocarcinoma was present in 16, carcinoid tumor in 1 and both adenocarcinoma and carcinoid tumor in 1 patient. Stage I and Stage II were the most common (66.7% and 22.2%, respectively). Majority of the tumors were in the right upper lobe (55.6%). There were 7 healthy controls with a median age of 29 years (28-43) and 71% females. There was a significantly increased proportion of MO-MDSCs in NSCLC patients preoperatively compared to healthy controls (11.64% versus 5.02%, p = 0.02). CCR2+CCR5+ MO-MDSCs were 0.85% in patients versus 0.06% in controls (p=0.04). No differences were noted with PMN-MDSCs. Five patients had post-operative follow up (mean 152 days) with an average decrease of 63% in MO-MDSCs, 68% in CCR2+CCR5+ MO-MDSCs and no recurrence of tumor on CT scans.
Conclusion: Early results of this on-going study demonstrate the detection of circulating CCR2+CCR5+ MO-MDSCs in the preoperative whole blood of NSCLC patients compared to healthy controls. Resection of the tumor is associated with a decrease of these MO-MDSCs after treatment. We are evaluating if any increase in CCR2+CCR5+ MO-MDSC in long term will allow us to use it as an adjuvant tool along with CT monitoring as a biomarker of residual or recurrent disease.
Citation Format: Hamza Khan, Anas Awan, Maria Shishikura, Carley Blevins, Kristen Rodgers, Yuping Mei, Wasay Nizam, Shun Ishiyama, Yun Chen, Richard Battafarano, Errol Bush, Stephen Broderick, Stephen Yang, Hajime Orita, Peng Huang, Ada Tam, Jinny Ha, Franck Housseau, Malcolm Brock. Monitoring of CCR2 and CCR5 expression on circulating myeloid derived suppressor cells (MDSCs) in non-small cell lung cancer as a correlate of minimum residual disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 271.