Lineage-dependent gene expression programs influence the immune landscape of colorectal cancer

Hae Ock Lee; Yourae Hong; Hakki Emre Etlioglu; Yong Beom Cho; Valentina Pomella; Ben Van den Bosch; Jasper Vanhecke; Sara Verbandt; Hyekyung Hong; Jae Woong Min; Nayoung Kim; Hye Hyeon Eum; Junbin Qian; Bram Boeckx; Diether Lambrechts; Petros Tsantoulis; Gert De Hertogh; Woosung Chung; Taeseob Lee; Minae An; Hyun Tae Shin; Je Gun Joung; Min Hyeok Jung; Gunhwan Ko; Pratyaksha Wirapati; Seok Hyung Kim; Hee Cheol Kim; Seong Hyeon Yun; Iain Bee Huat Tan; Bobby Ranjan; Woo Yong Lee; Tae You Kim; Jung Kyoon Choi; Young Joon Kim; Shyam Prabhakar; Sabine Tejpar; Woong Yang Park

doi:10.1038/s41588-020-0636-z

Lineage-dependent gene expression programs influence the immune landscape of colorectal cancer

Hae Ock Lee, Yourae Hong, Hakki Emre Etlioglu, Yong Beom Cho, Valentina Pomella, Ben Van den Bosch, Jasper Vanhecke, Sara Verbandt, Hyekyung Hong, Jae Woong Min, Nayoung Kim, Hye Hyeon Eum, Junbin Qian, Bram Boeckx, Diether Lambrechts, Petros Tsantoulis, Gert De Hertogh, Woosung Chung, Taeseob Lee, Minae AnHyun Tae Shin, Je Gun Joung, Min Hyeok Jung, Gunhwan Ko, Pratyaksha Wirapati, Seok Hyung Kim, Hee Cheol Kim, Seong Hyeon Yun, Iain Bee Huat Tan, Bobby Ranjan, Woo Yong Lee, Tae You Kim, Jung Kyoon Choi, Young Joon Kim, Shyam Prabhakar, Sabine Tejpar, Woong Yang Park

Department of Microbiology

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

451 Scopus citations

Abstract

Immunotherapy for metastatic colorectal cancer is effective only for mismatch repair-deficient tumors with high microsatellite instability that demonstrate immune infiltration, suggesting that tumor cells can determine their immune microenvironment. To understand this cross-talk, we analyzed the transcriptome of 91,103 unsorted single cells from 23 Korean and 6 Belgian patients. Cancer cells displayed transcriptional features reminiscent of normal differentiation programs, and genetic alterations that apparently fostered immunosuppressive microenvironments directed by regulatory T cells, myofibroblasts and myeloid cells. Intercellular network reconstruction supported the association between cancer cell signatures and specific stromal or immune cell populations. Our collective view of the cellular landscape and intercellular interactions in colorectal cancer provide mechanistic information for the design of efficient immuno-oncology treatment strategies.

Original language	English
Pages (from-to)	594-603
Number of pages	10
Journal	Nature Genetics
Volume	52
Issue number	6
DOIs	https://doi.org/10.1038/s41588-020-0636-z
State	Published - 1 Jun 2020

Bibliographical note

Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.

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Lee, H. O., Hong, Y., Etlioglu, H. E., Cho, Y. B., Pomella, V., Van den Bosch, B., Vanhecke, J., Verbandt, S., Hong, H., Min, J. W., Kim, N., Eum, H. H., Qian, J., Boeckx, B., Lambrechts, D., Tsantoulis, P., De Hertogh, G., Chung, W., Lee, T., ... Park, W. Y. (2020). Lineage-dependent gene expression programs influence the immune landscape of colorectal cancer. Nature Genetics, 52(6), 594-603. https://doi.org/10.1038/s41588-020-0636-z

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title = "Lineage-dependent gene expression programs influence the immune landscape of colorectal cancer",

abstract = "Immunotherapy for metastatic colorectal cancer is effective only for mismatch repair-deficient tumors with high microsatellite instability that demonstrate immune infiltration, suggesting that tumor cells can determine their immune microenvironment. To understand this cross-talk, we analyzed the transcriptome of 91,103 unsorted single cells from 23 Korean and 6 Belgian patients. Cancer cells displayed transcriptional features reminiscent of normal differentiation programs, and genetic alterations that apparently fostered immunosuppressive microenvironments directed by regulatory T cells, myofibroblasts and myeloid cells. Intercellular network reconstruction supported the association between cancer cell signatures and specific stromal or immune cell populations. Our collective view of the cellular landscape and intercellular interactions in colorectal cancer provide mechanistic information for the design of efficient immuno-oncology treatment strategies.",

author = "Lee, {Hae Ock} and Yourae Hong and Etlioglu, {Hakki Emre} and Cho, {Yong Beom} and Valentina Pomella and {Van den Bosch}, Ben and Jasper Vanhecke and Sara Verbandt and Hyekyung Hong and Min, {Jae Woong} and Nayoung Kim and Eum, {Hye Hyeon} and Junbin Qian and Bram Boeckx and Diether Lambrechts and Petros Tsantoulis and {De Hertogh}, Gert and Woosung Chung and Taeseob Lee and Minae An and Shin, {Hyun Tae} and Joung, {Je Gun} and Jung, {Min Hyeok} and Gunhwan Ko and Pratyaksha Wirapati and Kim, {Seok Hyung} and Kim, {Hee Cheol} and Yun, {Seong Hyeon} and Tan, {Iain Bee Huat} and Bobby Ranjan and Lee, {Woo Yong} and Kim, {Tae You} and Choi, {Jung Kyoon} and Kim, {Young Joon} and Shyam Prabhakar and Sabine Tejpar and Park, {Woong Yang}",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2020",

month = jun,

day = "1",

doi = "10.1038/s41588-020-0636-z",

language = "English",

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Lee, HO, Hong, Y, Etlioglu, HE, Cho, YB, Pomella, V, Van den Bosch, B, Vanhecke, J, Verbandt, S, Hong, H, Min, JW, Kim, N, Eum, HH, Qian, J, Boeckx, B, Lambrechts, D, Tsantoulis, P, De Hertogh, G, Chung, W, Lee, T, An, M, Shin, HT, Joung, JG, Jung, MH, Ko, G, Wirapati, P, Kim, SH, Kim, HC, Yun, SH, Tan, IBH, Ranjan, B, Lee, WY, Kim, TY, Choi, JK, Kim, YJ, Prabhakar, S, Tejpar, S & Park, WY 2020, 'Lineage-dependent gene expression programs influence the immune landscape of colorectal cancer', Nature Genetics, vol. 52, no. 6, pp. 594-603. https://doi.org/10.1038/s41588-020-0636-z

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AU - Lee, Hae Ock

AU - Hong, Yourae

AU - Etlioglu, Hakki Emre

AU - Cho, Yong Beom

AU - Pomella, Valentina

AU - Van den Bosch, Ben

AU - Vanhecke, Jasper

AU - Verbandt, Sara

AU - Hong, Hyekyung

AU - Min, Jae Woong

AU - Kim, Nayoung

AU - Eum, Hye Hyeon

AU - Qian, Junbin

AU - Boeckx, Bram

AU - Lambrechts, Diether

AU - Tsantoulis, Petros

AU - De Hertogh, Gert

AU - Chung, Woosung

AU - Lee, Taeseob

AU - An, Minae

AU - Shin, Hyun Tae

AU - Joung, Je Gun

AU - Jung, Min Hyeok

AU - Ko, Gunhwan

AU - Wirapati, Pratyaksha

AU - Kim, Seok Hyung

AU - Kim, Hee Cheol

AU - Yun, Seong Hyeon

AU - Tan, Iain Bee Huat

AU - Ranjan, Bobby

AU - Lee, Woo Yong

AU - Kim, Tae You

AU - Choi, Jung Kyoon

AU - Kim, Young Joon

AU - Prabhakar, Shyam

AU - Tejpar, Sabine

AU - Park, Woong Yang

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AB - Immunotherapy for metastatic colorectal cancer is effective only for mismatch repair-deficient tumors with high microsatellite instability that demonstrate immune infiltration, suggesting that tumor cells can determine their immune microenvironment. To understand this cross-talk, we analyzed the transcriptome of 91,103 unsorted single cells from 23 Korean and 6 Belgian patients. Cancer cells displayed transcriptional features reminiscent of normal differentiation programs, and genetic alterations that apparently fostered immunosuppressive microenvironments directed by regulatory T cells, myofibroblasts and myeloid cells. Intercellular network reconstruction supported the association between cancer cell signatures and specific stromal or immune cell populations. Our collective view of the cellular landscape and intercellular interactions in colorectal cancer provide mechanistic information for the design of efficient immuno-oncology treatment strategies.

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DO - 10.1038/s41588-020-0636-z

M3 - Article

C2 - 32451460

AN - SCOPUS:85085343999

SN - 1061-4036

VL - 52

SP - 594

EP - 603

JO - Nature Genetics

JF - Nature Genetics

IS - 6

ER -

Lineage-dependent gene expression programs influence the immune landscape of colorectal cancer

Abstract

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