The role of the immunoescape in colorectal cancer liver metastasis.

The expression of programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) indicate the efficacy of anti-PD-1/PD-L1 therapy in colorectal cancer (CRC), but are less useful for monitoring the efficacy of therapy of CRC liver metastasis (CRLM). This study investigated the effects of immune mole...

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Autores principales:	Chie Takasu, Shoko Yamashita, Yuji Morine, Kozo Yoshikawa, Takuya Tokunaga, Masaaki Nishi, Hideya Kashihara, Toshiaki Yoshimoto, Mitsuo Shimada
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3511fdeea96f4b9781757d9dba0b3b81
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spelling	oai:doaj.org-article:3511fdeea96f4b9781757d9dba0b3b812021-12-02T20:12:38ZThe role of the immunoescape in colorectal cancer liver metastasis.1932-620310.1371/journal.pone.0259940https://doaj.org/article/3511fdeea96f4b9781757d9dba0b3b812021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0259940https://doaj.org/toc/1932-6203The expression of programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) indicate the efficacy of anti-PD-1/PD-L1 therapy in colorectal cancer (CRC), but are less useful for monitoring the efficacy of therapy of CRC liver metastasis (CRLM). This study investigated the effects of immune molecules on the prognosis of CRLM. We enrolled 71 patients with CRLM who underwent curative resection for CRC. We used immunohistochemistry to analyze the expression of PD-1, PD-L1, indoleamine-pyrrole 2,3-dioxygenase (IDO), and CD163 (a marker of tumor-associated macrophages [TAMs]) in metastatic tumors. The immune molecules PD-1, PD-L1, IDO, and TAMs were expressed in 32.3%, 47.8%, 45.0%, and 47.9% of metastatic CRC samples, respectively. The 5-year overall survival rates associated with immune molecule-positive groups were significantly better than in the negative groups (PD-1: 87.7% vs 53.2%, p = 0.023; PD-L1: 82.4% vs 42.3%, p = 0.007; IDO: 80.7% vs 43.5%, p = 0.007; TAMs: 82.6% vs 48.0%, p = 0.005). Multivariate analysis revealed PD-1 expression (p = 0.032, hazard ratio: 0.19), IDO expression (p = 0.049, hazard ratio: 0.37), and tumor differentiation (p<0.001, hazard ratio: 0.02) as independent prognostic indicators. PD-1 and TAMs in metastases were associated with less aggressive features such as smaller tumors. Furthermore, TAMs positively and significantly correlated with PD-1 expression (p = 0.011), PD-L1 expression (p = 0.024), and tended to correlate with IDO expression (p = 0.078). PD-1, PD-L1, IDO, and TAMs in CRLM were associated with less aggressive features and better prognosis of patients with CRC, indicating adaptive antitumor immunity vs immune tolerance. These molecules may therefore serve as prognostic markers for CRLM.Chie TakasuShoko YamashitaYuji MorineKozo YoshikawaTakuya TokunagaMasaaki NishiHideya KashiharaToshiaki YoshimotoMitsuo ShimadaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11, p e0259940 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chie Takasu Shoko Yamashita Yuji Morine Kozo Yoshikawa Takuya Tokunaga Masaaki Nishi Hideya Kashihara Toshiaki Yoshimoto Mitsuo Shimada The role of the immunoescape in colorectal cancer liver metastasis.
description	The expression of programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) indicate the efficacy of anti-PD-1/PD-L1 therapy in colorectal cancer (CRC), but are less useful for monitoring the efficacy of therapy of CRC liver metastasis (CRLM). This study investigated the effects of immune molecules on the prognosis of CRLM. We enrolled 71 patients with CRLM who underwent curative resection for CRC. We used immunohistochemistry to analyze the expression of PD-1, PD-L1, indoleamine-pyrrole 2,3-dioxygenase (IDO), and CD163 (a marker of tumor-associated macrophages [TAMs]) in metastatic tumors. The immune molecules PD-1, PD-L1, IDO, and TAMs were expressed in 32.3%, 47.8%, 45.0%, and 47.9% of metastatic CRC samples, respectively. The 5-year overall survival rates associated with immune molecule-positive groups were significantly better than in the negative groups (PD-1: 87.7% vs 53.2%, p = 0.023; PD-L1: 82.4% vs 42.3%, p = 0.007; IDO: 80.7% vs 43.5%, p = 0.007; TAMs: 82.6% vs 48.0%, p = 0.005). Multivariate analysis revealed PD-1 expression (p = 0.032, hazard ratio: 0.19), IDO expression (p = 0.049, hazard ratio: 0.37), and tumor differentiation (p<0.001, hazard ratio: 0.02) as independent prognostic indicators. PD-1 and TAMs in metastases were associated with less aggressive features such as smaller tumors. Furthermore, TAMs positively and significantly correlated with PD-1 expression (p = 0.011), PD-L1 expression (p = 0.024), and tended to correlate with IDO expression (p = 0.078). PD-1, PD-L1, IDO, and TAMs in CRLM were associated with less aggressive features and better prognosis of patients with CRC, indicating adaptive antitumor immunity vs immune tolerance. These molecules may therefore serve as prognostic markers for CRLM.
format	article
author	Chie Takasu Shoko Yamashita Yuji Morine Kozo Yoshikawa Takuya Tokunaga Masaaki Nishi Hideya Kashihara Toshiaki Yoshimoto Mitsuo Shimada
author_facet	Chie Takasu Shoko Yamashita Yuji Morine Kozo Yoshikawa Takuya Tokunaga Masaaki Nishi Hideya Kashihara Toshiaki Yoshimoto Mitsuo Shimada
author_sort	Chie Takasu
title	The role of the immunoescape in colorectal cancer liver metastasis.
title_short	The role of the immunoescape in colorectal cancer liver metastasis.
title_full	The role of the immunoescape in colorectal cancer liver metastasis.
title_fullStr	The role of the immunoescape in colorectal cancer liver metastasis.
title_full_unstemmed	The role of the immunoescape in colorectal cancer liver metastasis.
title_sort	role of the immunoescape in colorectal cancer liver metastasis.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/3511fdeea96f4b9781757d9dba0b3b81
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The role of the immunoescape in colorectal cancer liver metastasis.

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