Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia

Matthew T. Witkowski; Igor Dolgalev; Nikki A. Evensen; Chao Ma; Tiffany Chambers; Kathryn G. Roberts; Sheetal Sreeram; Yuling Dai; Anastasia N. Tikhonova; Audrey Lasry; Chunxu Qu; Deqing Pei; Cheng Cheng; Gabriel A. Robbins; Joanna Pierro; Shanmugapriya Selvaraj; Valeria Mezzano; Marla Daves; Philip J. Lupo; Michael E. Scheurer; Cynthia A. Loomis; Charles G. Mullighan; Weiqiang Chen; Karen R. Rabin; Aristotelis Tsirigos; William L. Carroll; Iannis Aifantis

doi:10.1016/j.ccell.2020.04.015

Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia

Matthew T. Witkowski, Igor Dolgalev, Nikki A. Evensen, Chao Ma, Tiffany Chambers, Kathryn G. Roberts, Sheetal Sreeram, Yuling Dai, Anastasia N. Tikhonova, Audrey Lasry, Chunxu Qu, Deqing Pei, Cheng Cheng, Gabriel A. Robbins, Joanna Pierro, Shanmugapriya Selvaraj, Valeria Mezzano, Marla Daves, Philip J. Lupo, Michael E. ScheurerCynthia A. Loomis, Charles G. Mullighan, Weiqiang Chen, Karen R. Rabin, Aristotelis Tsirigos, William L. Carroll, Iannis Aifantis

Mechanical and Aerospace Engineering

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

Abstract

Using single-cell analysis of B cell acute lymphoblastic leukemia (B-ALL) patient samples, Witkowski et al. show that the frequency of non-classical monocytes predicts patient survival. Depletion of these monocytes improves treatment responsiveness in animal models of high-risk B-ALL.

Original language	English (US)
Pages (from-to)	867-882.e12
Journal	Cancer Cell
Volume	37
Issue number	6
DOIs	https://doi.org/10.1016/j.ccell.2020.04.015
State	Published - Jun 8 2020

Keywords

acute lymphoblastic leukemia
chemotherapy
immune microenvironment
monocytes
relapse
single cell

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

Access to Document

10.1016/j.ccell.2020.04.015

Cite this

Witkowski, M. T., Dolgalev, I., Evensen, N. A., Ma, C., Chambers, T., Roberts, K. G., Sreeram, S., Dai, Y., Tikhonova, A. N., Lasry, A., Qu, C., Pei, D., Cheng, C., Robbins, G. A., Pierro, J., Selvaraj, S., Mezzano, V., Daves, M., Lupo, P. J., ... Aifantis, I. (2020). Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia. Cancer Cell, 37(6), 867-882.e12. https://doi.org/10.1016/j.ccell.2020.04.015

Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia. / Witkowski, Matthew T.; Dolgalev, Igor; Evensen, Nikki A.; Ma, Chao; Chambers, Tiffany; Roberts, Kathryn G.; Sreeram, Sheetal; Dai, Yuling; Tikhonova, Anastasia N.; Lasry, Audrey; Qu, Chunxu; Pei, Deqing; Cheng, Cheng; Robbins, Gabriel A.; Pierro, Joanna; Selvaraj, Shanmugapriya; Mezzano, Valeria; Daves, Marla; Lupo, Philip J.; Scheurer, Michael E.; Loomis, Cynthia A.; Mullighan, Charles G.; Chen, Weiqiang; Rabin, Karen R.; Tsirigos, Aristotelis; Carroll, William L.; Aifantis, Iannis.

In: Cancer Cell, Vol. 37, No. 6, 08.06.2020, p. 867-882.e12.

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

Witkowski, MT, Dolgalev, I, Evensen, NA, Ma, C, Chambers, T, Roberts, KG, Sreeram, S, Dai, Y, Tikhonova, AN, Lasry, A, Qu, C, Pei, D, Cheng, C, Robbins, GA, Pierro, J, Selvaraj, S, Mezzano, V, Daves, M, Lupo, PJ, Scheurer, ME, Loomis, CA, Mullighan, CG, Chen, W, Rabin, KR, Tsirigos, A, Carroll, WL & Aifantis, I 2020, 'Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia', Cancer Cell, vol. 37, no. 6, pp. 867-882.e12. https://doi.org/10.1016/j.ccell.2020.04.015

Witkowski, Matthew T. ; Dolgalev, Igor ; Evensen, Nikki A. ; Ma, Chao ; Chambers, Tiffany ; Roberts, Kathryn G. ; Sreeram, Sheetal ; Dai, Yuling ; Tikhonova, Anastasia N. ; Lasry, Audrey ; Qu, Chunxu ; Pei, Deqing ; Cheng, Cheng ; Robbins, Gabriel A. ; Pierro, Joanna ; Selvaraj, Shanmugapriya ; Mezzano, Valeria ; Daves, Marla ; Lupo, Philip J. ; Scheurer, Michael E. ; Loomis, Cynthia A. ; Mullighan, Charles G. ; Chen, Weiqiang ; Rabin, Karen R. ; Tsirigos, Aristotelis ; Carroll, William L. ; Aifantis, Iannis. / Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia. In: Cancer Cell. 2020 ; Vol. 37, No. 6. pp. 867-882.e12.

@article{1a3e09e7cd41403ba6537256f2feece5,

title = "Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia",

abstract = "Using single-cell analysis of B cell acute lymphoblastic leukemia (B-ALL) patient samples, Witkowski et al. show that the frequency of non-classical monocytes predicts patient survival. Depletion of these monocytes improves treatment responsiveness in animal models of high-risk B-ALL.",

keywords = "acute lymphoblastic leukemia, chemotherapy, immune microenvironment, monocytes, relapse, single cell",

author = "Witkowski, {Matthew T.} and Igor Dolgalev and Evensen, {Nikki A.} and Chao Ma and Tiffany Chambers and Roberts, {Kathryn G.} and Sheetal Sreeram and Yuling Dai and Tikhonova, {Anastasia N.} and Audrey Lasry and Chunxu Qu and Deqing Pei and Cheng Cheng and Robbins, {Gabriel A.} and Joanna Pierro and Shanmugapriya Selvaraj and Valeria Mezzano and Marla Daves and Lupo, {Philip J.} and Scheurer, {Michael E.} and Loomis, {Cynthia A.} and Mullighan, {Charles G.} and Weiqiang Chen and Rabin, {Karen R.} and Aristotelis Tsirigos and Carroll, {William L.} and Iannis Aifantis",

note = "Funding Information: We thank the NYU School of Medicine core facilities, including High Performance Computing, Flow Cytometry and the Genome Technology Center (this shared resource is partially supported by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center). We are grateful to J. Rubnitz and M. Lear from St Jude Children's Hospital, and T. Tello, J. Lund, and Y.D. from the Children's Oncology Group for assistance with patient bone marrow biopsy acquisition. We are grateful to P. Chattopadhyay at the NYU Precision Immunology Incubator for assistance with the BD Symphony. We are grateful to the NYU Histopathology Core for assistance with primary human tissue sectioning and imaging, Y. Deng and M. Cammer from the NYU Langone's Microscopy Laboratory for assistance with imaging. We are grateful to B. Reizis for manuscript suggestions. Experimental Pathology Research Lab by the Cancer Center Support Grant P30CA016087 and the PerkinElmer Vectra multispectral imaging system awarded through a Shared Instrumentation Grant S10 OD021747. This research was supported by the US NIH (RO1CA202025, RO1CA202027, RO1CA216421, 1RO1CA228135, and PO1CA229086), the Leukemia & Lymphoma Society (TRP no. 6580), the Alex's Lemonade Stand Foundation for Childhood Cancer, and the St. Baldrick's Cancer Research Foundation (to I.A). M.W. is a Fellow of The Leukemia & Lymphoma Society. This project was supported by funds from The Jeffrey Pride Foundation for Pediatric Cancer Research and the Children's Oncology Group Foundation. The work was also supported by the New York State Department of Health (NYSTEM Program). A.N.T. was supported by the Leukemia and Lymphoma Society and the Alex's Lemonade Stand Foundation for Childhood Cancer. Figure S1A and Graphical Abstract generated using BioRender. Conceptualization, M.T.W. I.D. W.L.C. and I.A.; Methodology, M.T.W. I.D. N.A.E. A.N.T. C.M. K.G.R. C.A.L. K.R.R. and I.A.; Investigation, M.T.W. I.D. N.A.E. C.M. T.C. K.G.R. S.S. C.Q. D.P. C.C. V.M. M.E.S. Y.D. A.L. K.R.R. W.L.C. and I.A.; Resources, M.T.W. I.D. N.A.E. C.M. T.C. K.G.R. G.A.R. J.P. M.D. P.J.L. M.E.S. C.G.M. K.R.R. W.L.C. and I.A. Writing ? Original Draft, M.T.W. I.D. and I.A.; Writing ? Review & Editing, M.T.W. I.D. N.A.E. A.N.T. A.T. W.L.C. and I.A; Visualization, I.D. S.S. V.M. and C.A.L.; Supervision, A.T. W.L.C. and I.A. The authors declare no competing interests. Funding Information: We thank the NYU School of Medicine core facilities, including High Performance Computing, Flow Cytometry and the Genome Technology Center (this shared resource is partially supported by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center). We are grateful to J. Rubnitz and M. Lear from St Jude Children's Hospital, and T. Tello, J. Lund, and Y.D. from the Children's Oncology Group for assistance with patient bone marrow biopsy acquisition. We are grateful to P. Chattopadhyay at the NYU Precision Immunology Incubator for assistance with the BD Symphony. We are grateful to the NYU Histopathology Core for assistance with primary human tissue sectioning and imaging, Y. Deng and M. Cammer from the NYU Langone's Microscopy Laboratory for assistance with imaging. We are grateful to B. Reizis for manuscript suggestions. Experimental Pathology Research Lab by the Cancer Center Support Grant P30CA016087 and the PerkinElmer Vectra multispectral imaging system awarded through a Shared Instrumentation Grant S10 OD021747. This research was supported by the US NIH ( RO1CA202025 , RO1CA202027 , RO1CA216421 , 1RO1CA228135 , and PO1CA229086 ), the Leukemia & Lymphoma Society (TRP no. 6580), the Alex's Lemonade Stand Foundation for Childhood Cancer , and the St. Baldrick{\textquoteright}s Cancer Research Foundation (to I.A). M.W. is a Fellow of The Leukemia & Lymphoma Society. This project was supported by funds from The Jeffrey Pride Foundation for Pediatric Cancer Research and the Children{\textquoteright}s Oncology Group Foundation . The work was also supported by the New York State Department of Health (NYSTEM Program). A.N.T. was supported by the Leukemia and Lymphoma Society and the Alex's Lemonade Stand Foundation for Childhood Cancer . Figure S1A and Graphical Abstract generated using BioRender. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = jun,

day = "8",

doi = "10.1016/j.ccell.2020.04.015",

language = "English (US)",

volume = "37",

pages = "867--882.e12",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "6",

}

TY - JOUR

T1 - Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia

AU - Witkowski, Matthew T.

AU - Dolgalev, Igor

AU - Evensen, Nikki A.

AU - Ma, Chao

AU - Chambers, Tiffany

AU - Roberts, Kathryn G.

AU - Sreeram, Sheetal

AU - Dai, Yuling

AU - Tikhonova, Anastasia N.

AU - Lasry, Audrey

AU - Qu, Chunxu

AU - Pei, Deqing

AU - Cheng, Cheng

AU - Robbins, Gabriel A.

AU - Pierro, Joanna

AU - Selvaraj, Shanmugapriya

AU - Mezzano, Valeria

AU - Daves, Marla

AU - Lupo, Philip J.

AU - Scheurer, Michael E.

AU - Loomis, Cynthia A.

AU - Mullighan, Charles G.

AU - Chen, Weiqiang

AU - Rabin, Karen R.

AU - Tsirigos, Aristotelis

AU - Carroll, William L.

AU - Aifantis, Iannis

N1 - Funding Information: We thank the NYU School of Medicine core facilities, including High Performance Computing, Flow Cytometry and the Genome Technology Center (this shared resource is partially supported by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center). We are grateful to J. Rubnitz and M. Lear from St Jude Children's Hospital, and T. Tello, J. Lund, and Y.D. from the Children's Oncology Group for assistance with patient bone marrow biopsy acquisition. We are grateful to P. Chattopadhyay at the NYU Precision Immunology Incubator for assistance with the BD Symphony. We are grateful to the NYU Histopathology Core for assistance with primary human tissue sectioning and imaging, Y. Deng and M. Cammer from the NYU Langone's Microscopy Laboratory for assistance with imaging. We are grateful to B. Reizis for manuscript suggestions. Experimental Pathology Research Lab by the Cancer Center Support Grant P30CA016087 and the PerkinElmer Vectra multispectral imaging system awarded through a Shared Instrumentation Grant S10 OD021747. This research was supported by the US NIH (RO1CA202025, RO1CA202027, RO1CA216421, 1RO1CA228135, and PO1CA229086), the Leukemia & Lymphoma Society (TRP no. 6580), the Alex's Lemonade Stand Foundation for Childhood Cancer, and the St. Baldrick's Cancer Research Foundation (to I.A). M.W. is a Fellow of The Leukemia & Lymphoma Society. This project was supported by funds from The Jeffrey Pride Foundation for Pediatric Cancer Research and the Children's Oncology Group Foundation. The work was also supported by the New York State Department of Health (NYSTEM Program). A.N.T. was supported by the Leukemia and Lymphoma Society and the Alex's Lemonade Stand Foundation for Childhood Cancer. Figure S1A and Graphical Abstract generated using BioRender. Conceptualization, M.T.W. I.D. W.L.C. and I.A.; Methodology, M.T.W. I.D. N.A.E. A.N.T. C.M. K.G.R. C.A.L. K.R.R. and I.A.; Investigation, M.T.W. I.D. N.A.E. C.M. T.C. K.G.R. S.S. C.Q. D.P. C.C. V.M. M.E.S. Y.D. A.L. K.R.R. W.L.C. and I.A.; Resources, M.T.W. I.D. N.A.E. C.M. T.C. K.G.R. G.A.R. J.P. M.D. P.J.L. M.E.S. C.G.M. K.R.R. W.L.C. and I.A. Writing ? Original Draft, M.T.W. I.D. and I.A.; Writing ? Review & Editing, M.T.W. I.D. N.A.E. A.N.T. A.T. W.L.C. and I.A; Visualization, I.D. S.S. V.M. and C.A.L.; Supervision, A.T. W.L.C. and I.A. The authors declare no competing interests. Funding Information: We thank the NYU School of Medicine core facilities, including High Performance Computing, Flow Cytometry and the Genome Technology Center (this shared resource is partially supported by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center). We are grateful to J. Rubnitz and M. Lear from St Jude Children's Hospital, and T. Tello, J. Lund, and Y.D. from the Children's Oncology Group for assistance with patient bone marrow biopsy acquisition. We are grateful to P. Chattopadhyay at the NYU Precision Immunology Incubator for assistance with the BD Symphony. We are grateful to the NYU Histopathology Core for assistance with primary human tissue sectioning and imaging, Y. Deng and M. Cammer from the NYU Langone's Microscopy Laboratory for assistance with imaging. We are grateful to B. Reizis for manuscript suggestions. Experimental Pathology Research Lab by the Cancer Center Support Grant P30CA016087 and the PerkinElmer Vectra multispectral imaging system awarded through a Shared Instrumentation Grant S10 OD021747. This research was supported by the US NIH ( RO1CA202025 , RO1CA202027 , RO1CA216421 , 1RO1CA228135 , and PO1CA229086 ), the Leukemia & Lymphoma Society (TRP no. 6580), the Alex's Lemonade Stand Foundation for Childhood Cancer , and the St. Baldrick’s Cancer Research Foundation (to I.A). M.W. is a Fellow of The Leukemia & Lymphoma Society. This project was supported by funds from The Jeffrey Pride Foundation for Pediatric Cancer Research and the Children’s Oncology Group Foundation . The work was also supported by the New York State Department of Health (NYSTEM Program). A.N.T. was supported by the Leukemia and Lymphoma Society and the Alex's Lemonade Stand Foundation for Childhood Cancer . Figure S1A and Graphical Abstract generated using BioRender. Publisher Copyright: © 2020 Elsevier Inc.

PY - 2020/6/8

Y1 - 2020/6/8

N2 - Using single-cell analysis of B cell acute lymphoblastic leukemia (B-ALL) patient samples, Witkowski et al. show that the frequency of non-classical monocytes predicts patient survival. Depletion of these monocytes improves treatment responsiveness in animal models of high-risk B-ALL.

AB - Using single-cell analysis of B cell acute lymphoblastic leukemia (B-ALL) patient samples, Witkowski et al. show that the frequency of non-classical monocytes predicts patient survival. Depletion of these monocytes improves treatment responsiveness in animal models of high-risk B-ALL.

KW - acute lymphoblastic leukemia

KW - chemotherapy

KW - immune microenvironment

KW - monocytes

KW - relapse

KW - single cell

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UR - http://www.scopus.com/inward/citedby.url?scp=85085749879&partnerID=8YFLogxK

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DO - 10.1016/j.ccell.2020.04.015

M3 - Article

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SP - 867-882.e12

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 6

ER -

Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia

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