Abstract 3415: The neutrophil-to-lymphocyte ratio (NLR) reflects intratumor myeloid derived suppressor cell (MDSC) infiltration in metastatic castration-resistant prostate cancers (mCRPC)
Authors: Guo Christina , Rekowski Jan , Crespo Mateus , Gurel Bora , Yuan Wei , Sharp Adam , Grochot Rafael , Chandran Khobe , Sumanasuriya Semini , Ferreira Ana , Alimonti Andrea , de Bono Johann S. 
Published: June 2022

Abstract
Background: High neutrophil-to-lymphocyte ratio (NLR) associates with worse overall survival (OS) from prostate cancer (PC) and low response rates to abiraterone and taxane chemotherapy and may reflect systemic inflammatory changes. A direct link between high NLR and intratumoral myeloid infiltration has not been demonstrated to date. We evaluated the relationship between NLR and intratumor immune cell densities in mCRPC biopsies.
Design: mCRPC biopsies from 71 patients treated at The Institute of Cancer Research/Royal Marsden Hospital (ICR/RMH, UK) were stained by immunofluorescence for CD11b, CD15, and DAPI and by immunohistochemistry for CD3 to algorithmically quantify PMN-MDSC and T cell densities in the tumor and stromal compartments. NLR (neutrophil count divided by lymphocyte count), ALP, LDH, and albumin were obtained from blood collected contemporaneous with mCRPC biopsies. Clinical data were retrospectively collected. Negative binomial regression determined the association between leucocyte densities and log-transformed NLR. Modified Poisson regression estimated the risk ratio (RR) for the presence of PMN-MDSCs in relation to higher NLR (&gt;3). OS was analysed using Cox regression and Kaplan-Meier. RNAseq data from Stand Up 2 Cancer/Prostate Cancer Foundation (SU2C/PCF, n=159) and RMH cohorts (n=98) were analysed by Spearman’s correlation.
Results: NLR positively associated with the density of PMN-MDSCs infiltrating the tumor (p=0.0004) and stromal (p=0.0007) compartments of mCRPC biopsies as determined by Halo࣪ computational modelling. Tumors with high NLR were more likely to be infiltrated by PMN-MDSCs (RR: 1.41; 95% confidence interval [CI]: 1.04-1.92; p=0.03). NLR independently associated with worse OS from the time of mCRPC biopsy after adjusting for LDH, ALP, metastasis at the time of diagnosis, and albumin (HR: 1.71; 95% CI: 1.20-2.46). Patients with low NLR and an absence of tumor-infiltrating PMN-MDSC had longer OS than those with a high NLR, tumor-infiltrating PMN-MDSCs or a combination of both (p=0.015). Whilst there was no association between NLR or PMN-MDSC density and CD3 T cell density, RNAseq analyses of two independent CRPC cohorts showed that MDSC signatures strongly and positively associated with signatures of T cell terminal exhaustion (SU2C/PCF: rs=0.74; p&lt;1x10-6; RMH: rs=0.64; p&lt;1x10-6) providing credence for the impact of MDSCs on T effector function.
Conclusion: Peripheral blood NLR was positively correlated with prostate tumor-infiltrating PMN-MDSC density supporting the interaction between the circulating myeloid compartment and intratumoral myeloid infiltration in patients with advanced PC.
Citation Format: Christina Guo, Jan Rekowski, Mateus Crespo, Bora Gurel, Wei Yuan, Adam Sharp, Rafael Grochot, Khobe Chandran, Semini Sumanasuriya, Ana Ferreira, Andrea Alimonti, Johann S. de Bono. The neutrophil-to-lymphocyte ratio (NLR) reflects intratumor myeloid derived suppressor cell (MDSC) infiltration in metastatic castration-resistant prostate cancers (mCRPC) [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 3415.