Single-cell RNA sequencing to characterize the response of pancreatic cancer to anti-PD-1 immunotherapy

Pancreatic cancer (PaC) is resistant to immune checkpoint therapy, but the underlying mechanisms are largely unknown. In this study, we have established four orthotopic PaC murine models with different PaC cell lines by intra-pancreatic inoculation. Therapeutic examinations demonstrate that only tum...

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Autores principales:	Jing Zhou, Yuexu Jiang, Yue Huang, Qiongling Wang, Jussuf T. Kaifi, Eric T. Kimchi, Chiswili Yves Chabu, Zhenguo Liu, Trupti Joshi, Guangfu Li
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Pancreatic cancer (PaC) Single-cell sequencing (scRNA-seq) Programmed cell death protein 1 (PD-1) αPD-1 antibody (αPD-1 Ab) Tumor-associated macrophages (TAM) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/a21934920a644ea9857ba22b86db5b6e
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spelling	oai:doaj.org-article:a21934920a644ea9857ba22b86db5b6e2021-11-10T04:22:46ZSingle-cell RNA sequencing to characterize the response of pancreatic cancer to anti-PD-1 immunotherapy1936-523310.1016/j.tranon.2021.101262https://doaj.org/article/a21934920a644ea9857ba22b86db5b6e2022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1936523321002539https://doaj.org/toc/1936-5233Pancreatic cancer (PaC) is resistant to immune checkpoint therapy, but the underlying mechanisms are largely unknown. In this study, we have established four orthotopic PaC murine models with different PaC cell lines by intra-pancreatic inoculation. Therapeutic examinations demonstrate that only tumors induced with Panc02-H7 cells respond to αPD-1 antibody treatment, leading to significantly reduced tumor growth and increased survival in the recipient mice. Transcriptomic profiling at a single-cell resolution characterizes the molecular activity of different cells within tumors. Comparative analysis and validated experiments demonstrate that αPD-1-sensitive and -resistant tumors differently shape the immune landscape in the tumor microenvironment (TME) and markedly altering effector CD8+ T cells and tumor-associated macrophages (TAMs) in their number, frequency, and gene profile. More exhausted effector CD8+ T cells and increased M2-like TAMs with a reduced capacity of antigen presentation are detected in resistant Panc02-formed tumors versus responsive Panc02-H7-formed tumors. Together, our data highlight the correlation of tumor-induced imbalance of macrophages with the fate of tumor-resident effector CD8+ T cells and PaC response to αPD-1 immunotherapy. TAMs as a critical regulator of tumor immunity and immunotherapy contribute to PaC resistance to immune checkpoint blockade.Jing ZhouYuexu JiangYue HuangQiongling WangJussuf T. KaifiEric T. KimchiChiswili Yves ChabuZhenguo LiuTrupti JoshiGuangfu LiElsevierarticlePancreatic cancer (PaC)Single-cell sequencing (scRNA-seq)Programmed cell death protein 1 (PD-1)αPD-1 antibody (αPD-1 Ab)Tumor-associated macrophages (TAM)Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENTranslational Oncology, Vol 15, Iss 1, Pp 101262- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pancreatic cancer (PaC) Single-cell sequencing (scRNA-seq) Programmed cell death protein 1 (PD-1) αPD-1 antibody (αPD-1 Ab) Tumor-associated macrophages (TAM) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Pancreatic cancer (PaC) Single-cell sequencing (scRNA-seq) Programmed cell death protein 1 (PD-1) αPD-1 antibody (αPD-1 Ab) Tumor-associated macrophages (TAM) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jing Zhou Yuexu Jiang Yue Huang Qiongling Wang Jussuf T. Kaifi Eric T. Kimchi Chiswili Yves Chabu Zhenguo Liu Trupti Joshi Guangfu Li Single-cell RNA sequencing to characterize the response of pancreatic cancer to anti-PD-1 immunotherapy
description	Pancreatic cancer (PaC) is resistant to immune checkpoint therapy, but the underlying mechanisms are largely unknown. In this study, we have established four orthotopic PaC murine models with different PaC cell lines by intra-pancreatic inoculation. Therapeutic examinations demonstrate that only tumors induced with Panc02-H7 cells respond to αPD-1 antibody treatment, leading to significantly reduced tumor growth and increased survival in the recipient mice. Transcriptomic profiling at a single-cell resolution characterizes the molecular activity of different cells within tumors. Comparative analysis and validated experiments demonstrate that αPD-1-sensitive and -resistant tumors differently shape the immune landscape in the tumor microenvironment (TME) and markedly altering effector CD8+ T cells and tumor-associated macrophages (TAMs) in their number, frequency, and gene profile. More exhausted effector CD8+ T cells and increased M2-like TAMs with a reduced capacity of antigen presentation are detected in resistant Panc02-formed tumors versus responsive Panc02-H7-formed tumors. Together, our data highlight the correlation of tumor-induced imbalance of macrophages with the fate of tumor-resident effector CD8+ T cells and PaC response to αPD-1 immunotherapy. TAMs as a critical regulator of tumor immunity and immunotherapy contribute to PaC resistance to immune checkpoint blockade.
format	article
author	Jing Zhou Yuexu Jiang Yue Huang Qiongling Wang Jussuf T. Kaifi Eric T. Kimchi Chiswili Yves Chabu Zhenguo Liu Trupti Joshi Guangfu Li
author_facet	Jing Zhou Yuexu Jiang Yue Huang Qiongling Wang Jussuf T. Kaifi Eric T. Kimchi Chiswili Yves Chabu Zhenguo Liu Trupti Joshi Guangfu Li
author_sort	Jing Zhou
title	Single-cell RNA sequencing to characterize the response of pancreatic cancer to anti-PD-1 immunotherapy
title_short	Single-cell RNA sequencing to characterize the response of pancreatic cancer to anti-PD-1 immunotherapy
title_full	Single-cell RNA sequencing to characterize the response of pancreatic cancer to anti-PD-1 immunotherapy
title_fullStr	Single-cell RNA sequencing to characterize the response of pancreatic cancer to anti-PD-1 immunotherapy
title_full_unstemmed	Single-cell RNA sequencing to characterize the response of pancreatic cancer to anti-PD-1 immunotherapy
title_sort	single-cell rna sequencing to characterize the response of pancreatic cancer to anti-pd-1 immunotherapy
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/a21934920a644ea9857ba22b86db5b6e
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Single-cell RNA sequencing to characterize the response of pancreatic cancer to anti-PD-1 immunotherapy

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