Myeloid-derived suppressor cell subset accumulation in renal cell carcinoma parenchyma is associated with intratumoral expression of IL1b, IL8, CXCL5, and Mip-1α

Yana G. Najjar, Patricia Rayman, Xuefei Jia, Paul G. Pavicic, Brian I. Rini, Charles Tannenbaum, Jennifer Ko, Samuel Haywood, Peter A Cohen, Thomas Hamilton, C. Marcela Diaz-Montero, James Finke

Research output: Contribution to journalArticle

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Abstract

Purpose: Little is known about the association between myeloid- derived suppressor cell (MDSC) subsets and various chemokines in patients with renal cell carcinoma (RCC) or the factors that draw MDSC into tumor parenchyma. Experimental Design: We analyzed polymorphonuclear MDSC (PMN-MDSC), monocytic MDSC (M-MDSC), and immatureMDSC( I-MDSC) from the parenchyma and peripheral blood of 48 patients with RCC, isolated at nephrectomy. We analyzed levels of IL1β, IL8, CXCL5, Mip-1α, MCP-1, and Rantes. Furthermore, we performed experiments in a Renca murine model to assess therapeutic synergy between CXCR2 and anti-PD1 and to elucidate the impact of IL1β blockade on MDSC. Results: Parenchymal PMN-MDSC have a positive correlation with IL1β, IL8, CXCL5, and Mip-1α, and I-MDSC correlate with IL8 and CXCL5. Furthermore, peripheral PMN-MDSC correlate with tumor grade. Given that PMN-MDSC express CXCR2 and parenchymal PMN-MDSC correlated with IL8 and CXCL5, we assessed the response of CXCR2 blockade with or without anti- PD1. Combination therapy reduced tumor weight and enhanced CD4+ and CD8+ T-cell infiltration. In addition, anti-IL1β decreased PMN-MDSC and M-MDSC in the periphery, PMN-MDSC in the tumor, and peripheral CXCL5 and KC. Anti-IL1β also delayed tumor growth. Conclusions: Parenchymal PMN-MDSC have a positive correlation with IL1β, IL8, CXCL5, and Mip-1α, suggesting they may attract PMN-MDSC into the tumor. Peripheral PMNMDSC correlate with tumor grade, suggesting prognostic significance. Anti-CXCR2 and anti-PD1 synergized to reduce tumor weight and enhanced CD4+ and CD8+ T-cell infiltration in a Renca murine model, suggesting that CXCR2+ PMNMDSC are important in reducing activity of anti-PD1 antibody. Finally, anti-IL1β decreases MDSC and delayed tumor growth, suggesting a potential target for MDSC inhibition.

Original languageEnglish (US)
Pages (from-to)2346-2355
Number of pages10
JournalClinical Cancer Research
Volume23
Issue number9
DOIs
StatePublished - May 1 2017

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Interleukin-8
Renal Cell Carcinoma
Neoplasms
Myeloid-Derived Suppressor Cells
Tumor Burden
T-Lymphocytes
Growth
Nephrectomy
Chemokines
Anti-Idiotypic Antibodies
Research Design

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Myeloid-derived suppressor cell subset accumulation in renal cell carcinoma parenchyma is associated with intratumoral expression of IL1b, IL8, CXCL5, and Mip-1α. / Najjar, Yana G.; Rayman, Patricia; Jia, Xuefei; Pavicic, Paul G.; Rini, Brian I.; Tannenbaum, Charles; Ko, Jennifer; Haywood, Samuel; Cohen, Peter A; Hamilton, Thomas; Diaz-Montero, C. Marcela; Finke, James.

In: Clinical Cancer Research, Vol. 23, No. 9, 01.05.2017, p. 2346-2355.

Research output: Contribution to journalArticle

Najjar, YG, Rayman, P, Jia, X, Pavicic, PG, Rini, BI, Tannenbaum, C, Ko, J, Haywood, S, Cohen, PA, Hamilton, T, Diaz-Montero, CM & Finke, J 2017, 'Myeloid-derived suppressor cell subset accumulation in renal cell carcinoma parenchyma is associated with intratumoral expression of IL1b, IL8, CXCL5, and Mip-1α', Clinical Cancer Research, vol. 23, no. 9, pp. 2346-2355. https://doi.org/10.1158/1078-0432.CCR-15-1823
Najjar, Yana G. ; Rayman, Patricia ; Jia, Xuefei ; Pavicic, Paul G. ; Rini, Brian I. ; Tannenbaum, Charles ; Ko, Jennifer ; Haywood, Samuel ; Cohen, Peter A ; Hamilton, Thomas ; Diaz-Montero, C. Marcela ; Finke, James. / Myeloid-derived suppressor cell subset accumulation in renal cell carcinoma parenchyma is associated with intratumoral expression of IL1b, IL8, CXCL5, and Mip-1α. In: Clinical Cancer Research. 2017 ; Vol. 23, No. 9. pp. 2346-2355.
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abstract = "Purpose: Little is known about the association between myeloid- derived suppressor cell (MDSC) subsets and various chemokines in patients with renal cell carcinoma (RCC) or the factors that draw MDSC into tumor parenchyma. Experimental Design: We analyzed polymorphonuclear MDSC (PMN-MDSC), monocytic MDSC (M-MDSC), and immatureMDSC( I-MDSC) from the parenchyma and peripheral blood of 48 patients with RCC, isolated at nephrectomy. We analyzed levels of IL1β, IL8, CXCL5, Mip-1α, MCP-1, and Rantes. Furthermore, we performed experiments in a Renca murine model to assess therapeutic synergy between CXCR2 and anti-PD1 and to elucidate the impact of IL1β blockade on MDSC. Results: Parenchymal PMN-MDSC have a positive correlation with IL1β, IL8, CXCL5, and Mip-1α, and I-MDSC correlate with IL8 and CXCL5. Furthermore, peripheral PMN-MDSC correlate with tumor grade. Given that PMN-MDSC express CXCR2 and parenchymal PMN-MDSC correlated with IL8 and CXCL5, we assessed the response of CXCR2 blockade with or without anti- PD1. Combination therapy reduced tumor weight and enhanced CD4+ and CD8+ T-cell infiltration. In addition, anti-IL1β decreased PMN-MDSC and M-MDSC in the periphery, PMN-MDSC in the tumor, and peripheral CXCL5 and KC. Anti-IL1β also delayed tumor growth. Conclusions: Parenchymal PMN-MDSC have a positive correlation with IL1β, IL8, CXCL5, and Mip-1α, suggesting they may attract PMN-MDSC into the tumor. Peripheral PMNMDSC correlate with tumor grade, suggesting prognostic significance. Anti-CXCR2 and anti-PD1 synergized to reduce tumor weight and enhanced CD4+ and CD8+ T-cell infiltration in a Renca murine model, suggesting that CXCR2+ PMNMDSC are important in reducing activity of anti-PD1 antibody. Finally, anti-IL1β decreases MDSC and delayed tumor growth, suggesting a potential target for MDSC inhibition.",
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T1 - Myeloid-derived suppressor cell subset accumulation in renal cell carcinoma parenchyma is associated with intratumoral expression of IL1b, IL8, CXCL5, and Mip-1α

AU - Najjar, Yana G.

AU - Rayman, Patricia

AU - Jia, Xuefei

AU - Pavicic, Paul G.

AU - Rini, Brian I.

AU - Tannenbaum, Charles

AU - Ko, Jennifer

AU - Haywood, Samuel

AU - Cohen, Peter A

AU - Hamilton, Thomas

AU - Diaz-Montero, C. Marcela

AU - Finke, James

PY - 2017/5/1

Y1 - 2017/5/1

N2 - Purpose: Little is known about the association between myeloid- derived suppressor cell (MDSC) subsets and various chemokines in patients with renal cell carcinoma (RCC) or the factors that draw MDSC into tumor parenchyma. Experimental Design: We analyzed polymorphonuclear MDSC (PMN-MDSC), monocytic MDSC (M-MDSC), and immatureMDSC( I-MDSC) from the parenchyma and peripheral blood of 48 patients with RCC, isolated at nephrectomy. We analyzed levels of IL1β, IL8, CXCL5, Mip-1α, MCP-1, and Rantes. Furthermore, we performed experiments in a Renca murine model to assess therapeutic synergy between CXCR2 and anti-PD1 and to elucidate the impact of IL1β blockade on MDSC. Results: Parenchymal PMN-MDSC have a positive correlation with IL1β, IL8, CXCL5, and Mip-1α, and I-MDSC correlate with IL8 and CXCL5. Furthermore, peripheral PMN-MDSC correlate with tumor grade. Given that PMN-MDSC express CXCR2 and parenchymal PMN-MDSC correlated with IL8 and CXCL5, we assessed the response of CXCR2 blockade with or without anti- PD1. Combination therapy reduced tumor weight and enhanced CD4+ and CD8+ T-cell infiltration. In addition, anti-IL1β decreased PMN-MDSC and M-MDSC in the periphery, PMN-MDSC in the tumor, and peripheral CXCL5 and KC. Anti-IL1β also delayed tumor growth. Conclusions: Parenchymal PMN-MDSC have a positive correlation with IL1β, IL8, CXCL5, and Mip-1α, suggesting they may attract PMN-MDSC into the tumor. Peripheral PMNMDSC correlate with tumor grade, suggesting prognostic significance. Anti-CXCR2 and anti-PD1 synergized to reduce tumor weight and enhanced CD4+ and CD8+ T-cell infiltration in a Renca murine model, suggesting that CXCR2+ PMNMDSC are important in reducing activity of anti-PD1 antibody. Finally, anti-IL1β decreases MDSC and delayed tumor growth, suggesting a potential target for MDSC inhibition.

AB - Purpose: Little is known about the association between myeloid- derived suppressor cell (MDSC) subsets and various chemokines in patients with renal cell carcinoma (RCC) or the factors that draw MDSC into tumor parenchyma. Experimental Design: We analyzed polymorphonuclear MDSC (PMN-MDSC), monocytic MDSC (M-MDSC), and immatureMDSC( I-MDSC) from the parenchyma and peripheral blood of 48 patients with RCC, isolated at nephrectomy. We analyzed levels of IL1β, IL8, CXCL5, Mip-1α, MCP-1, and Rantes. Furthermore, we performed experiments in a Renca murine model to assess therapeutic synergy between CXCR2 and anti-PD1 and to elucidate the impact of IL1β blockade on MDSC. Results: Parenchymal PMN-MDSC have a positive correlation with IL1β, IL8, CXCL5, and Mip-1α, and I-MDSC correlate with IL8 and CXCL5. Furthermore, peripheral PMN-MDSC correlate with tumor grade. Given that PMN-MDSC express CXCR2 and parenchymal PMN-MDSC correlated with IL8 and CXCL5, we assessed the response of CXCR2 blockade with or without anti- PD1. Combination therapy reduced tumor weight and enhanced CD4+ and CD8+ T-cell infiltration. In addition, anti-IL1β decreased PMN-MDSC and M-MDSC in the periphery, PMN-MDSC in the tumor, and peripheral CXCL5 and KC. Anti-IL1β also delayed tumor growth. Conclusions: Parenchymal PMN-MDSC have a positive correlation with IL1β, IL8, CXCL5, and Mip-1α, suggesting they may attract PMN-MDSC into the tumor. Peripheral PMNMDSC correlate with tumor grade, suggesting prognostic significance. Anti-CXCR2 and anti-PD1 synergized to reduce tumor weight and enhanced CD4+ and CD8+ T-cell infiltration in a Renca murine model, suggesting that CXCR2+ PMNMDSC are important in reducing activity of anti-PD1 antibody. Finally, anti-IL1β decreases MDSC and delayed tumor growth, suggesting a potential target for MDSC inhibition.

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