Myeloid-derived-supressor cells as regulators of th eimmune system

C.L. Jones; Gintaras Sudzius; Diana Mieliauskaite; Almantas Siaurys; Rita Viliene; Irena Butrimiene; Dainius Characiejus; Irena Dumalakiene; Vernon C. Maino; Holden T. Maecker; Dong Wang; Guangyu An; Shengzhi Xie; Yajuan Yao; Guosheng Feng; E C Wang; P J Lehner; Deborah S Cunninghame Graham; L K Borysiewicz; Justin Lewis; Tammy Speers; Pilar Brito-Zerón; Hoda Gheitasi; Soledad Retamozo; Albert Bové; María C. Londoño; Jose-Maria Sánchez-Tapias; Miguel Caballero; Belchin Kostov; Xavier Forns; Srini V Kaveri; Manuel Ramos-Casals; Yazan S. Khaled; Basil J. Ammori; Eyad Elkord; Diana Mieliauskaite; Irena Dumalakiene; Gintaras Sudzius; Ieva Narkeviciute; Bianca Rovati; S Mariucci; M Manzoni; K Bencardino; M Danova; Susanna Hausmann-muela; Joan Muela Ribera; Elizabeth Toomer; Koen Peeters Grietens; Claudia A. Dumitru; Katrin Moses; Sokratis Trellakis; Stephan Lang; Sven Brandau; Frédéric Coutant; Pierre Miossec; Anum Fayyaz; Biji T. Kurien; R. Hal Scofield; G. HERNANDEZ-MOLINA; C. AVILA-CASADO; F. CARDENAS-VELAZQUEZ; Carlos Andres Hernandez Garcia; M. L. CALDERILLO; V. MARROQUIN; V. SOTO-ABRAHAM; C. RECILLAS-GISPERT; J. SANCHEZ-GUERRERO; Shaye Kivity; Maria Teresa Arango; Michael Ehrenfeld; Omer Tehori; Yehuda Shoenfeld; Juan Manuel Anaya; Nancy Agmon-Levin; K E Aziz; P J McCluskey; D Wakefield; Gintaras Sudzius; Diana Mieliauskaite; Almantas Siaurys; Rita Viliene; Irena Butrimiene; Dainius Characiejus; Irena Dumalakiene; Davide Lucchesi; Costantino Pitzalis; Michele Bombardieri; Arnaud Dupuy D'Angeac; Serge Monier; Darrell Pilling; Adolfo Travaglio-Encinoza; Thierry Rème; Mike Salmon; Dörte Hamann; Marijke Th.L Roos; René a.W van Lier; Daniele Focosi; Marco Bestagno; Oscar Burrone; Mario Petrini; Ryo Okada; Takaaki Kondo; Fumichika Matsuki; Hiroshi Takata; Masafumi Takiguchi; Jill M Kramer; Samantha Solito; Ilaria Marigo; Laura Pinton; Vera Damuzzo; Susanna Mandruzzato; Vincenzo Bronte; Tim F Greten; Michael P Manns; Firouzeh Korangy; Author Manuscript; Byung Ha Lee; Adrienne E. Gauna; Kaleb M. Pauley; Yun-Jong Park; Seunghee Cha

doi:https://www.nature.com/articles/nri2506

Myeloid-derived-supressor cells as regulators of th eimmune system

C.L. Jones, Gintaras Sudzius, Diana Mieliauskaite, Almantas Siaurys, Rita Viliene, Irena Butrimiene, Dainius Characiejus, Irena Dumalakiene, Vernon C. Maino, Holden T. Maecker, Dong Wang, Guangyu An, Shengzhi Xie, Yajuan Yao, Guosheng Feng, E C Wang, P J Lehner, Deborah S Cunninghame Graham, L K Borysiewicz, Justin LewisTammy Speers, Pilar Brito-Zerón, Hoda Gheitasi, Soledad Retamozo, Albert Bové, María C. Londoño, Jose-Maria Sánchez-Tapias, Miguel Caballero, Belchin Kostov, Xavier Forns, Srini V Kaveri, Manuel Ramos-Casals, Yazan S. Khaled, Basil J. Ammori, Eyad Elkord, Diana Mieliauskaite, Irena Dumalakiene, Gintaras Sudzius, Ieva Narkeviciute, Bianca Rovati, S Mariucci, M Manzoni, K Bencardino, M Danova, Susanna Hausmann-muela, Joan Muela Ribera, Elizabeth Toomer, Koen Peeters Grietens, Claudia A. Dumitru, Katrin Moses, Sokratis Trellakis, Stephan Lang, Sven Brandau, Frédéric Coutant, Pierre Miossec, Anum Fayyaz, Biji T. Kurien, R. Hal Scofield, G. HERNANDEZ-MOLINA, C. AVILA-CASADO, F. CARDENAS-VELAZQUEZ, Carlos Andres Hernandez Garcia, M. L. CALDERILLO, V. MARROQUIN, V. SOTO-ABRAHAM, C. RECILLAS-GISPERT, J. SANCHEZ-GUERRERO, Shaye Kivity, Maria Teresa Arango, Michael Ehrenfeld, Omer Tehori, Yehuda Shoenfeld, Juan Manuel Anaya, Nancy Agmon-Levin, K E Aziz, P J McCluskey, D Wakefield, Gintaras Sudzius, Diana Mieliauskaite, Almantas Siaurys, Rita Viliene, Irena Butrimiene, Dainius Characiejus, Irena Dumalakiene, Davide Lucchesi, Costantino Pitzalis, Michele Bombardieri, Arnaud Dupuy D'Angeac, Serge Monier, Darrell Pilling, Adolfo Travaglio-Encinoza, Thierry Rème, Mike Salmon, Dörte Hamann, Marijke Th.L Roos, René a.W van Lier, Daniele Focosi, Marco Bestagno, Oscar Burrone, Mario Petrini, Ryo Okada, Takaaki Kondo, Fumichika Matsuki, Hiroshi Takata, Masafumi Takiguchi, Jill M Kramer, Samantha Solito, Ilaria Marigo, Laura Pinton, Vera Damuzzo, Susanna Mandruzzato, Vincenzo Bronte, Tim F Greten, Michael P Manns, Firouzeh Korangy, Author Manuscript, Byung Ha Lee, Adrienne E. Gauna, Kaleb M. Pauley, Yun-Jong Park, Seunghee Cha

Center for Autoimmune Diseases Research (CREA)

Research output: Contribution to journal › Article › peer-review

244 Scopus citations

Abstract

In tumor-bearing mice, immunosuppressive granulocytic and monocytic MDSC have been identified. The identity and function of MDSC in cancer patients are less clear and need further characterization. We analyzed the peripheral blood of 103 patients with HNC, lung cancer, or cancers of bladder and ureter. Based on sedimentation properties in density gradients, a subset of LD-PMN was identified and analyzed. LD-PMN were expanded in the peripheral blood of cancer patients, suppressed proliferation, and IFN-γ production of polyclonally stimulated T cells and thus, qualify as human MDSC. Immunophenotyping and morphological analysis revealed the accumulation of immature PMN in the MDSC fraction. Neutrophilic MDSC showed altered surface marker expression, prolonged survival, and impaired effector functions when compared with conventional, mature PMN of regular density. MDSC displayed markedly reduced chemotaxis toward tumor-conditioned medium and lacked expression of chemokine receptors CXCR1 and CXCR2, which are normally required for PMN extravasation from the bloodstream and subsequent tissue infiltration. Collectively, our data suggest the accumulation and persistence of long-lived, immature granulocytic MDSC with T cell-suppressive function and impaired migratory properties in the peripheral blood of cancer patients.

Original language	English (US)
Pages (from-to)	162-174
Number of pages	12
Journal	Nature Reviews Immunology
Volume	9
DOIs	https://doi.org/https://www.nature.com/articles/nri2506
State	Published - Mar 1 2009

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Jones, C. L., Sudzius, G., Mieliauskaite, D., Siaurys, A., Viliene, R., Butrimiene, I., Characiejus, D., Dumalakiene, I., Maino, V. C., Maecker, H. T., Wang, D., An, G., Xie, S., Yao, Y., Feng, G., Wang, E. C., Lehner, P. J., Graham, D. S. C., Borysiewicz, L. K., ... Cha, S. (2009). Myeloid-derived-supressor cells as regulators of th eimmune system. Nature Reviews Immunology, 9, 162-174. https://doi.org/https://www.nature.com/articles/nri2506

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title = "Myeloid-derived-supressor cells as regulators of th eimmune system",

abstract = "In tumor-bearing mice, immunosuppressive granulocytic and monocytic MDSC have been identified. The identity and function of MDSC in cancer patients are less clear and need further characterization. We analyzed the peripheral blood of 103 patients with HNC, lung cancer, or cancers of bladder and ureter. Based on sedimentation properties in density gradients, a subset of LD-PMN was identified and analyzed. LD-PMN were expanded in the peripheral blood of cancer patients, suppressed proliferation, and IFN-γ production of polyclonally stimulated T cells and thus, qualify as human MDSC. Immunophenotyping and morphological analysis revealed the accumulation of immature PMN in the MDSC fraction. Neutrophilic MDSC showed altered surface marker expression, prolonged survival, and impaired effector functions when compared with conventional, mature PMN of regular density. MDSC displayed markedly reduced chemotaxis toward tumor-conditioned medium and lacked expression of chemokine receptors CXCR1 and CXCR2, which are normally required for PMN extravasation from the bloodstream and subsequent tissue infiltration. Collectively, our data suggest the accumulation and persistence of long-lived, immature granulocytic MDSC with T cell-suppressive function and impaired migratory properties in the peripheral blood of cancer patients.",

author = "C.L. Jones and Gintaras Sudzius and Diana Mieliauskaite and Almantas Siaurys and Rita Viliene and Irena Butrimiene and Dainius Characiejus and Irena Dumalakiene and Maino, {Vernon C.} and Maecker, {Holden T.} and Dong Wang and Guangyu An and Shengzhi Xie and Yajuan Yao and Guosheng Feng and Wang, {E C} and Lehner, {P J} and Graham, {Deborah S Cunninghame} and Borysiewicz, {L K} and Justin Lewis and Tammy Speers and Pilar Brito-Zer{\'o}n and Hoda Gheitasi and Soledad Retamozo and Albert Bov{\'e} and Londo{\~n}o, {Mar{\'i}a C.} and Jose-Maria S{\'a}nchez-Tapias and Miguel Caballero and Belchin Kostov and Xavier Forns and Kaveri, {Srini V} and Manuel Ramos-Casals and Khaled, {Yazan S.} and Ammori, {Basil J.} and Eyad Elkord and Diana Mieliauskaite and Irena Dumalakiene and Gintaras Sudzius and Ieva Narkeviciute and Bianca Rovati and S Mariucci and M Manzoni and K Bencardino and M Danova and Susanna Hausmann-muela and Ribera, {Joan Muela} and Elizabeth Toomer and Grietens, {Koen Peeters} and Dumitru, {Claudia A.} and Katrin Moses and Sokratis Trellakis and Stephan Lang and Sven Brandau and Fr{\'e}d{\'e}ric Coutant and Pierre Miossec and Anum Fayyaz and Kurien, {Biji T.} and Scofield, {R. Hal} and G. HERNANDEZ-MOLINA and C. AVILA-CASADO and F. CARDENAS-VELAZQUEZ and {Hernandez Garcia}, {Carlos Andres} and CALDERILLO, {M. L.} and V. MARROQUIN and V. SOTO-ABRAHAM and C. RECILLAS-GISPERT and J. SANCHEZ-GUERRERO and Shaye Kivity and Arango, {Maria Teresa} and Michael Ehrenfeld and Omer Tehori and Yehuda Shoenfeld and Anaya, {Juan Manuel} and Nancy Agmon-Levin and Aziz, {K E} and McCluskey, {P J} and D Wakefield and Gintaras Sudzius and Diana Mieliauskaite and Almantas Siaurys and Rita Viliene and Irena Butrimiene and Dainius Characiejus and Irena Dumalakiene and Davide Lucchesi and Costantino Pitzalis and Michele Bombardieri and D'Angeac, {Arnaud Dupuy} and Serge Monier and Darrell Pilling and Adolfo Travaglio-Encinoza and Thierry R{\`e}me and Mike Salmon and D{\"o}rte Hamann and Roos, {Marijke Th.L} and {van Lier}, {Ren{\'e} a.W} and Daniele Focosi and Marco Bestagno and Oscar Burrone and Mario Petrini and Ryo Okada and Takaaki Kondo and Fumichika Matsuki and Hiroshi Takata and Masafumi Takiguchi and Kramer, {Jill M} and Samantha Solito and Ilaria Marigo and Laura Pinton and Vera Damuzzo and Susanna Mandruzzato and Vincenzo Bronte and Greten, {Tim F} and Manns, {Michael P} and Firouzeh Korangy and Author Manuscript and Lee, {Byung Ha} and Gauna, {Adrienne E.} and Pauley, {Kaleb M.} and Yun-Jong Park and Seunghee Cha",

year = "2009",

month = mar,

day = "1",

doi = "https://www.nature.com/articles/nri2506",

language = "English (US)",

volume = "9",

pages = "162--174",

journal = "Nature Reviews Immunology",

issn = "1474-1733",

publisher = "Nature Publishing Group",

}

Jones, CL, Sudzius, G, Mieliauskaite, D, Siaurys, A, Viliene, R, Butrimiene, I, Characiejus, D, Dumalakiene, I, Maino, VC, Maecker, HT, Wang, D, An, G, Xie, S, Yao, Y, Feng, G, Wang, EC, Lehner, PJ, Graham, DSC, Borysiewicz, LK, Lewis, J, Speers, T, Brito-Zerón, P, Gheitasi, H, Retamozo, S, Bové, A, Londoño, MC, Sánchez-Tapias, J-M, Caballero, M, Kostov, B, Forns, X, Kaveri, SV, Ramos-Casals, M, Khaled, YS, Ammori, BJ, Elkord, E, Mieliauskaite, D, Dumalakiene, I, Sudzius, G, Narkeviciute, I, Rovati, B, Mariucci, S, Manzoni, M, Bencardino, K, Danova, M, Hausmann-muela, S, Ribera, JM, Toomer, E, Grietens, KP, Dumitru, CA, Moses, K, Trellakis, S, Lang, S, Brandau, S, Coutant, F, Miossec, P, Fayyaz, A, Kurien, BT, Scofield, RH, HERNANDEZ-MOLINA, G, AVILA-CASADO, C, CARDENAS-VELAZQUEZ, F, Hernandez Garcia, CA, CALDERILLO, ML, MARROQUIN, V, SOTO-ABRAHAM, V, RECILLAS-GISPERT, C, SANCHEZ-GUERRERO, J, Kivity, S, Arango, MT, Ehrenfeld, M, Tehori, O, Shoenfeld, Y, Anaya, JM, Agmon-Levin, N, Aziz, KE, McCluskey, PJ, Wakefield, D, Sudzius, G, Mieliauskaite, D, Siaurys, A, Viliene, R, Butrimiene, I, Characiejus, D, Dumalakiene, I, Lucchesi, D, Pitzalis, C, Bombardieri, M, D'Angeac, AD, Monier, S, Pilling, D, Travaglio-Encinoza, A, Rème, T, Salmon, M, Hamann, D, Roos, MTL, van Lier, RAW, Focosi, D, Bestagno, M, Burrone, O, Petrini, M, Okada, R, Kondo, T, Matsuki, F, Takata, H, Takiguchi, M, Kramer, JM, Solito, S, Marigo, I, Pinton, L, Damuzzo, V, Mandruzzato, S, Bronte, V, Greten, TF, Manns, MP, Korangy, F, Manuscript, A, Lee, BH, Gauna, AE, Pauley, KM, Park, Y-J & Cha, S 2009, 'Myeloid-derived-supressor cells as regulators of th eimmune system', Nature Reviews Immunology, vol. 9, pp. 162-174. https://doi.org/https://www.nature.com/articles/nri2506

TY - JOUR

T1 - Myeloid-derived-supressor cells as regulators of th eimmune system

AU - Jones, C.L.

AU - Sudzius, Gintaras

AU - Mieliauskaite, Diana

AU - Siaurys, Almantas

AU - Viliene, Rita

AU - Butrimiene, Irena

AU - Characiejus, Dainius

AU - Dumalakiene, Irena

AU - Maino, Vernon C.

AU - Maecker, Holden T.

AU - Wang, Dong

AU - An, Guangyu

AU - Xie, Shengzhi

AU - Yao, Yajuan

AU - Feng, Guosheng

AU - Wang, E C

AU - Lehner, P J

AU - Graham, Deborah S Cunninghame

AU - Borysiewicz, L K

AU - Lewis, Justin

AU - Speers, Tammy

AU - Brito-Zerón, Pilar

AU - Gheitasi, Hoda

AU - Retamozo, Soledad

AU - Bové, Albert

AU - Londoño, María C.

AU - Sánchez-Tapias, Jose-Maria

AU - Caballero, Miguel

AU - Kostov, Belchin

AU - Forns, Xavier

AU - Kaveri, Srini V

AU - Ramos-Casals, Manuel

AU - Khaled, Yazan S.

AU - Ammori, Basil J.

AU - Elkord, Eyad

AU - Mieliauskaite, Diana

AU - Dumalakiene, Irena

AU - Sudzius, Gintaras

AU - Narkeviciute, Ieva

AU - Rovati, Bianca

AU - Mariucci, S

AU - Manzoni, M

AU - Bencardino, K

AU - Danova, M

AU - Hausmann-muela, Susanna

AU - Ribera, Joan Muela

AU - Toomer, Elizabeth

AU - Grietens, Koen Peeters

AU - Dumitru, Claudia A.

AU - Moses, Katrin

AU - Trellakis, Sokratis

AU - Lang, Stephan

AU - Brandau, Sven

AU - Coutant, Frédéric

AU - Miossec, Pierre

AU - Fayyaz, Anum

AU - Kurien, Biji T.

AU - Scofield, R. Hal

AU - HERNANDEZ-MOLINA, G.

AU - AVILA-CASADO, C.

AU - CARDENAS-VELAZQUEZ, F.

AU - Hernandez Garcia, Carlos Andres

AU - CALDERILLO, M. L.

AU - MARROQUIN, V.

AU - SOTO-ABRAHAM, V.

AU - RECILLAS-GISPERT, C.

AU - SANCHEZ-GUERRERO, J.

AU - Kivity, Shaye

AU - Arango, Maria Teresa

AU - Ehrenfeld, Michael

AU - Tehori, Omer

AU - Shoenfeld, Yehuda

AU - Anaya, Juan Manuel

AU - Agmon-Levin, Nancy

AU - Aziz, K E

AU - McCluskey, P J

AU - Wakefield, D

AU - Sudzius, Gintaras

AU - Mieliauskaite, Diana

AU - Siaurys, Almantas

AU - Viliene, Rita

AU - Butrimiene, Irena

AU - Characiejus, Dainius

AU - Dumalakiene, Irena

AU - Lucchesi, Davide

AU - Pitzalis, Costantino

AU - Bombardieri, Michele

AU - D'Angeac, Arnaud Dupuy

AU - Monier, Serge

AU - Pilling, Darrell

AU - Travaglio-Encinoza, Adolfo

AU - Rème, Thierry

AU - Salmon, Mike

AU - Hamann, Dörte

AU - Roos, Marijke Th.L

AU - van Lier, René a.W

AU - Focosi, Daniele

AU - Bestagno, Marco

AU - Burrone, Oscar

AU - Petrini, Mario

AU - Okada, Ryo

AU - Kondo, Takaaki

AU - Matsuki, Fumichika

AU - Takata, Hiroshi

AU - Takiguchi, Masafumi

AU - Kramer, Jill M

AU - Solito, Samantha

AU - Marigo, Ilaria

AU - Pinton, Laura

AU - Damuzzo, Vera

AU - Mandruzzato, Susanna

AU - Bronte, Vincenzo

AU - Greten, Tim F

AU - Manns, Michael P

AU - Korangy, Firouzeh

AU - Manuscript, Author

AU - Lee, Byung Ha

AU - Gauna, Adrienne E.

AU - Pauley, Kaleb M.

AU - Park, Yun-Jong

AU - Cha, Seunghee

PY - 2009/3/1

Y1 - 2009/3/1

N2 - In tumor-bearing mice, immunosuppressive granulocytic and monocytic MDSC have been identified. The identity and function of MDSC in cancer patients are less clear and need further characterization. We analyzed the peripheral blood of 103 patients with HNC, lung cancer, or cancers of bladder and ureter. Based on sedimentation properties in density gradients, a subset of LD-PMN was identified and analyzed. LD-PMN were expanded in the peripheral blood of cancer patients, suppressed proliferation, and IFN-γ production of polyclonally stimulated T cells and thus, qualify as human MDSC. Immunophenotyping and morphological analysis revealed the accumulation of immature PMN in the MDSC fraction. Neutrophilic MDSC showed altered surface marker expression, prolonged survival, and impaired effector functions when compared with conventional, mature PMN of regular density. MDSC displayed markedly reduced chemotaxis toward tumor-conditioned medium and lacked expression of chemokine receptors CXCR1 and CXCR2, which are normally required for PMN extravasation from the bloodstream and subsequent tissue infiltration. Collectively, our data suggest the accumulation and persistence of long-lived, immature granulocytic MDSC with T cell-suppressive function and impaired migratory properties in the peripheral blood of cancer patients.

AB - In tumor-bearing mice, immunosuppressive granulocytic and monocytic MDSC have been identified. The identity and function of MDSC in cancer patients are less clear and need further characterization. We analyzed the peripheral blood of 103 patients with HNC, lung cancer, or cancers of bladder and ureter. Based on sedimentation properties in density gradients, a subset of LD-PMN was identified and analyzed. LD-PMN were expanded in the peripheral blood of cancer patients, suppressed proliferation, and IFN-γ production of polyclonally stimulated T cells and thus, qualify as human MDSC. Immunophenotyping and morphological analysis revealed the accumulation of immature PMN in the MDSC fraction. Neutrophilic MDSC showed altered surface marker expression, prolonged survival, and impaired effector functions when compared with conventional, mature PMN of regular density. MDSC displayed markedly reduced chemotaxis toward tumor-conditioned medium and lacked expression of chemokine receptors CXCR1 and CXCR2, which are normally required for PMN extravasation from the bloodstream and subsequent tissue infiltration. Collectively, our data suggest the accumulation and persistence of long-lived, immature granulocytic MDSC with T cell-suppressive function and impaired migratory properties in the peripheral blood of cancer patients.

U2 - https://www.nature.com/articles/nri2506

DO - https://www.nature.com/articles/nri2506

M3 - Article

C2 - 21106641

SN - 1474-1733

VL - 9

SP - 162

EP - 174

JO - Nature Reviews Immunology

JF - Nature Reviews Immunology

ER -

Myeloid-derived-supressor cells as regulators of th eimmune system

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