Skip to main content
Erschienen in: Cancer Immunology, Immunotherapy 9/2018

04.07.2018 | Original Article

Levels of peripheral blood polymorphonuclear myeloid-derived suppressor cells and selected cytokines are potentially prognostic of disease progression for patients with non-small cell lung cancer

verfasst von: Lourdes Barrera, Edgar Montes-Servín, Juan-Manuel Hernandez-Martinez, Mario Orozco-Morales, Elizabeth Montes-Servín, David Michel-Tello, Renato Augusto Morales-Flores, Diana Flores-Estrada, Oscar Arrieta

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 9/2018

Einloggen, um Zugang zu erhalten

Abstract

Polymorphonuclear-MDSC (PMN-MDSC) have emerged as an independent prognostic factor for survival in NSCLC. Similarly, cytokine profiles have been used to identify subgroups of NSCLC patients with different clinical outcomes. This prospective study investigated whether the percentage of circulating PMN-MDSC, in conjunction with the levels of plasma cytokines, was more informative of disease progression than the analysis of either factor alone. We analyzed the phenotypic and functional profile of peripheral blood T-cell subsets (CD3+, CD3+CD4+ and CD3+CD8+), neutrophils (CD66b+) and polymorphonuclear-MDSC (PMN-MDSC; CD66b+CD11b+CD15+CD14-) as well as the concentration of 14 plasma cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 p70, IL-17A, IL-27, IL-29, IL-31, and IL-33, TNF-α, IFN-γ) in 90 treatment-naïve NSCLC patients and 25 healthy donors (HD). In contrast to HD, NSCLC patients had a higher percentage of PMN-MDSC and neutrophils (P < 0.0001) but a lower percentage of CD3+, CD3+CD4+ and CD3+CD8+ cells. PMN-MDSC% negatively correlated with the levels of IL1-β, IL-2, IL-27 and IL-29. Two groups of patients were identified according to the percentage of circulating PMN-MDSC. Patients with low PMN-MDSC (≤ 8%) had a better OS (22.1 months [95% CI 4.3–739.7]) than patients with high PMN-MDSC (9.3 months [95% CI 0–18.8]). OS was significantly different among groups of patients stratified by both PMN-MDSC% and cytokine levels. In sum, our findings provide evidence suggesting that PMN-MDSC% in conjunction with the levels IL-1β, IL-27, and IL-29 could be a useful strategy to identify groups of patients with potentially unfavorable prognoses.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
10.
Zurück zum Zitat Kusmartsev S, Cheng F, Yu B, Nefedova Y, Sotomayor E, Lush R, Gabrilovich D (2003) All-trans-retinoic acid eliminates immature myeloid cells from tumor-bearing mice and improves the effect of vaccination. Cancer Res 63:4441–4449PubMed Kusmartsev S, Cheng F, Yu B, Nefedova Y, Sotomayor E, Lush R, Gabrilovich D (2003) All-trans-retinoic acid eliminates immature myeloid cells from tumor-bearing mice and improves the effect of vaccination. Cancer Res 63:4441–4449PubMed
17.
20.
Zurück zum Zitat Liu CY, Wang YM, Wang CL et al (2010) Population alterations of L-arginase- and inducible nitric oxide synthase-expressed CD11b+/CD14(−)/CD15+/CD33+ myeloid-derived suppressor cells and CD8+T lymphocytes in patients with advanced-stage non-small cell lung cancer. J Cancer Res Clin Oncol 136:35–45. https://doi.org/10.1007/s00432-009-0634-0 CrossRefPubMed Liu CY, Wang YM, Wang CL et al (2010) Population alterations of L-arginase- and inducible nitric oxide synthase-expressed CD11b+/CD14(−)/CD15+/CD33+ myeloid-derived suppressor cells and CD8+T lymphocytes in patients with advanced-stage non-small cell lung cancer. J Cancer Res Clin Oncol 136:35–45. https://​doi.​org/​10.​1007/​s00432-009-0634-0 CrossRefPubMed
23.
Zurück zum Zitat Almand B, Clark JI, Nikitina E, van Beynen J, English NR, Knight SC, Carbone DP, Gabrilovich DI (2001) Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol 166:678–689CrossRefPubMed Almand B, Clark JI, Nikitina E, van Beynen J, English NR, Knight SC, Carbone DP, Gabrilovich DI (2001) Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol 166:678–689CrossRefPubMed
29.
Zurück zum Zitat Barrera L, Montes-Servin E, Barrera A, Ramirez-Tirado LA, Salinas-Parra F, Banales-Mendez JL, Sandoval-Rios M, Arrieta O (2015) Cytokine profile determined by data-mining analysis set into clusters of non-small-cell lung cancer patients according to prognosis. Ann Oncol 26:428–435. https://doi.org/10.1093/annonc/mdu549 CrossRefPubMed Barrera L, Montes-Servin E, Barrera A, Ramirez-Tirado LA, Salinas-Parra F, Banales-Mendez JL, Sandoval-Rios M, Arrieta O (2015) Cytokine profile determined by data-mining analysis set into clusters of non-small-cell lung cancer patients according to prognosis. Ann Oncol 26:428–435. https://​doi.​org/​10.​1093/​annonc/​mdu549 CrossRefPubMed
30.
33.
Zurück zum Zitat Tomita M, Shimizu T, Ayabe T, Yonei A, Onitsuka T (2011) Preoperative neutrophil to lymphocyte ratio as a prognostic predictor after curative resection for non-small cell lung cancer. Anticancer Res 31:2995–2998PubMed Tomita M, Shimizu T, Ayabe T, Yonei A, Onitsuka T (2011) Preoperative neutrophil to lymphocyte ratio as a prognostic predictor after curative resection for non-small cell lung cancer. Anticancer Res 31:2995–2998PubMed
43.
Zurück zum Zitat Grossman SA, Ellsworth S, Campian J, Wild AT, Herman JM, Laheru D, Brock M, Balmanoukian A, Ye X (2015) Survival in patients with severe lymphopenia following treatment with radiation and chemotherapy for newly diagnosed solid tumors. J Natl Compr Cancer Netw JNCCN 13:1225–1231CrossRef Grossman SA, Ellsworth S, Campian J, Wild AT, Herman JM, Laheru D, Brock M, Balmanoukian A, Ye X (2015) Survival in patients with severe lymphopenia following treatment with radiation and chemotherapy for newly diagnosed solid tumors. J Natl Compr Cancer Netw JNCCN 13:1225–1231CrossRef
44.
Zurück zum Zitat Arrieta O, Michel Ortega RM, Villanueva-Rodriguez G, Serna-Thome MG, Flores-Estrada D, Diaz-Romero C, Rodriguez CM, Martinez L, Sanchez-Lara K (2010) Association of nutritional status and serum albumin levels with development of toxicity in patients with advanced non-small cell lung cancer treated with paclitaxel-cisplatin chemotherapy: a prospective study. BMC Cancer 10:50. https://doi.org/10.1186/1471-2407-10-50 CrossRefPubMedPubMedCentral Arrieta O, Michel Ortega RM, Villanueva-Rodriguez G, Serna-Thome MG, Flores-Estrada D, Diaz-Romero C, Rodriguez CM, Martinez L, Sanchez-Lara K (2010) Association of nutritional status and serum albumin levels with development of toxicity in patients with advanced non-small cell lung cancer treated with paclitaxel-cisplatin chemotherapy: a prospective study. BMC Cancer 10:50. https://​doi.​org/​10.​1186/​1471-2407-10-50 CrossRefPubMedPubMedCentral
49.
Zurück zum Zitat Song X, Krelin Y, Dvorkin T, Bjorkdahl O, Segal S, Dinarello CA, Voronov E, Apte RN (2005) CD11b+/Gr-1 + immature myeloid cells mediate suppression of T cells in mice bearing tumors of IL-1beta-secreting cells. J Immunol 175:8200–8208CrossRefPubMed Song X, Krelin Y, Dvorkin T, Bjorkdahl O, Segal S, Dinarello CA, Voronov E, Apte RN (2005) CD11b+/Gr-1 + immature myeloid cells mediate suppression of T cells in mice bearing tumors of IL-1beta-secreting cells. J Immunol 175:8200–8208CrossRefPubMed
53.
57.
59.
63.
Zurück zum Zitat Mattei F, Schiavoni G, Sestili P et al (2012) IRF-8 controls melanoma progression by regulating the cross talk between cancer and immune cells within the tumor microenvironment. Neoplasia 14:1223–1235CrossRefPubMedPubMedCentral Mattei F, Schiavoni G, Sestili P et al (2012) IRF-8 controls melanoma progression by regulating the cross talk between cancer and immune cells within the tumor microenvironment. Neoplasia 14:1223–1235CrossRefPubMedPubMedCentral
64.
Zurück zum Zitat Diakowska D, Lewandowski A, Markocka-Maczka K, Grabowski K (2013) Concentration of serum interleukin-27 increase in patients with lymph node metastatic gastroesophageal cancer. Adv Clin Exp Med 22:683–691PubMed Diakowska D, Lewandowski A, Markocka-Maczka K, Grabowski K (2013) Concentration of serum interleukin-27 increase in patients with lymph node metastatic gastroesophageal cancer. Adv Clin Exp Med 22:683–691PubMed
70.
Zurück zum Zitat Arrieta O, Morales-Flores R, Garcia-Vicente A, Montes-Servin E, Salinas-Parra F, Barrera L (2015) ORAL41.03 myeloid derived suppressor cells and their clinical relevance in non-small cell lung cancer. J Thorac Oncol 10(9):S255 Arrieta O, Morales-Flores R, Garcia-Vicente A, Montes-Servin E, Salinas-Parra F, Barrera L (2015) ORAL41.03 myeloid derived suppressor cells and their clinical relevance in non-small cell lung cancer. J Thorac Oncol 10(9):S255
Metadaten
Titel
Levels of peripheral blood polymorphonuclear myeloid-derived suppressor cells and selected cytokines are potentially prognostic of disease progression for patients with non-small cell lung cancer
verfasst von
Lourdes Barrera
Edgar Montes-Servín
Juan-Manuel Hernandez-Martinez
Mario Orozco-Morales
Elizabeth Montes-Servín
David Michel-Tello
Renato Augusto Morales-Flores
Diana Flores-Estrada
Oscar Arrieta
Publikationsdatum
04.07.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 9/2018
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-018-2196-y

Weitere Artikel der Ausgabe 9/2018

Cancer Immunology, Immunotherapy 9/2018 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.