Frequency of Apoptosis of Tumor-infiltrating Lymphocytes Induced by Fas Counterattack in Human Colorectal Carcinoma and Its Correlation with Prognosis

We investigated apoptosis in tumor-infiltrating lymphocytes (TILs) obtained from 41 colorectal carcinomas by in situ nick translation (ISNT). When the ISNT labeling index (LI) was determined as the number of positive nuclei per 1000 nuclei of TIL in tissue sections, the median LI was 12.0 (range, 2–...

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Veröffentlicht in:Clinical cancer research 2000-09, Vol.6 (9), p.3560-3564
Hauptverfasser: OKADA, Kazuya, KOMUTA, Ko, HASHIMOTO, Satoshi, MATSUZAKI, Sumihiro, KANEMATSU, Takashi, KOJI, Takehiko
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container_end_page 3564
container_issue 9
container_start_page 3560
container_title Clinical cancer research
container_volume 6
creator OKADA, Kazuya
KOMUTA, Ko
HASHIMOTO, Satoshi
MATSUZAKI, Sumihiro
KANEMATSU, Takashi
KOJI, Takehiko
description We investigated apoptosis in tumor-infiltrating lymphocytes (TILs) obtained from 41 colorectal carcinomas by in situ nick translation (ISNT). When the ISNT labeling index (LI) was determined as the number of positive nuclei per 1000 nuclei of TIL in tissue sections, the median LI was 12.0 (range, 2–30). The ISNT LI of colorectal carcinoma with lymph node metastasis was higher than that of colorectal carcinoma without metastasis. The cases with a high LI of ≥12.0 had a significantly poorer prognosis than those with a low LI. We also confirmed immunohistochemically that a part of the TILs expressed Fas using the sections adjacent to what contained abundant ISNT-positive TILs. Moreover, Fas ligand (FasL) expression was detected on the cell surface as well as the cytoplasm of colorectal cancer cells in 61% of cases. Apoptosis in TILs was consistently seen more frequently in FasL-positive cases than in FasL-negative ones. These findings indicate that the FasL expressed in colorectal carcinoma cells may kill the Fas-positive immune effective TILs by means of a Fas-FasL system termed Fas counterattack. This tumor immune evasion induced by FasL may therefore affect the malignant potential of human colorectal carcinoma.
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When the ISNT labeling index (LI) was determined as the number of positive nuclei per 1000 nuclei of TIL in tissue sections, the median LI was 12.0 (range, 2–30). The ISNT LI of colorectal carcinoma with lymph node metastasis was higher than that of colorectal carcinoma without metastasis. The cases with a high LI of ≥12.0 had a significantly poorer prognosis than those with a low LI. We also confirmed immunohistochemically that a part of the TILs expressed Fas using the sections adjacent to what contained abundant ISNT-positive TILs. Moreover, Fas ligand (FasL) expression was detected on the cell surface as well as the cytoplasm of colorectal cancer cells in 61% of cases. Apoptosis in TILs was consistently seen more frequently in FasL-positive cases than in FasL-negative ones. These findings indicate that the FasL expressed in colorectal carcinoma cells may kill the Fas-positive immune effective TILs by means of a Fas-FasL system termed Fas counterattack. This tumor immune evasion induced by FasL may therefore affect the malignant potential of human colorectal carcinoma.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>PMID: 10999744</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Apoptosis - physiology ; Biological and medical sciences ; Colorectal Neoplasms - immunology ; Colorectal Neoplasms - pathology ; DNA Fragmentation ; Fas Ligand Protein ; fas Receptor - biosynthesis ; fas Receptor - immunology ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating - cytology ; Lymphocytes, Tumor-Infiltrating - immunology ; Male ; Medical sciences ; Membrane Glycoproteins - biosynthesis ; Membrane Glycoproteins - immunology ; Middle Aged ; Prognosis ; Staining and Labeling - methods ; Stomach. Duodenum. 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When the ISNT labeling index (LI) was determined as the number of positive nuclei per 1000 nuclei of TIL in tissue sections, the median LI was 12.0 (range, 2–30). The ISNT LI of colorectal carcinoma with lymph node metastasis was higher than that of colorectal carcinoma without metastasis. The cases with a high LI of ≥12.0 had a significantly poorer prognosis than those with a low LI. We also confirmed immunohistochemically that a part of the TILs expressed Fas using the sections adjacent to what contained abundant ISNT-positive TILs. Moreover, Fas ligand (FasL) expression was detected on the cell surface as well as the cytoplasm of colorectal cancer cells in 61% of cases. Apoptosis in TILs was consistently seen more frequently in FasL-positive cases than in FasL-negative ones. These findings indicate that the FasL expressed in colorectal carcinoma cells may kill the Fas-positive immune effective TILs by means of a Fas-FasL system termed Fas counterattack. This tumor immune evasion induced by FasL may therefore affect the malignant potential of human colorectal carcinoma.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Apoptosis - physiology</subject><subject>Biological and medical sciences</subject><subject>Colorectal Neoplasms - immunology</subject><subject>Colorectal Neoplasms - pathology</subject><subject>DNA Fragmentation</subject><subject>Fas Ligand Protein</subject><subject>fas Receptor - biosynthesis</subject><subject>fas Receptor - immunology</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Lymphocytes, Tumor-Infiltrating - cytology</subject><subject>Lymphocytes, Tumor-Infiltrating - immunology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Membrane Glycoproteins - biosynthesis</subject><subject>Membrane Glycoproteins - immunology</subject><subject>Middle Aged</subject><subject>Prognosis</subject><subject>Staining and Labeling - methods</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. 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Anus</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>OKADA, Kazuya</creatorcontrib><creatorcontrib>KOMUTA, Ko</creatorcontrib><creatorcontrib>HASHIMOTO, Satoshi</creatorcontrib><creatorcontrib>MATSUZAKI, Sumihiro</creatorcontrib><creatorcontrib>KANEMATSU, Takashi</creatorcontrib><creatorcontrib>KOJI, Takehiko</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>OKADA, Kazuya</au><au>KOMUTA, Ko</au><au>HASHIMOTO, Satoshi</au><au>MATSUZAKI, Sumihiro</au><au>KANEMATSU, Takashi</au><au>KOJI, Takehiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Frequency of Apoptosis of Tumor-infiltrating Lymphocytes Induced by Fas Counterattack in Human Colorectal Carcinoma and Its Correlation with Prognosis</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2000-09-01</date><risdate>2000</risdate><volume>6</volume><issue>9</issue><spage>3560</spage><epage>3564</epage><pages>3560-3564</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>We investigated apoptosis in tumor-infiltrating lymphocytes (TILs) obtained from 41 colorectal carcinomas by in situ nick translation (ISNT). When the ISNT labeling index (LI) was determined as the number of positive nuclei per 1000 nuclei of TIL in tissue sections, the median LI was 12.0 (range, 2–30). The ISNT LI of colorectal carcinoma with lymph node metastasis was higher than that of colorectal carcinoma without metastasis. The cases with a high LI of ≥12.0 had a significantly poorer prognosis than those with a low LI. We also confirmed immunohistochemically that a part of the TILs expressed Fas using the sections adjacent to what contained abundant ISNT-positive TILs. Moreover, Fas ligand (FasL) expression was detected on the cell surface as well as the cytoplasm of colorectal cancer cells in 61% of cases. Apoptosis in TILs was consistently seen more frequently in FasL-positive cases than in FasL-negative ones. These findings indicate that the FasL expressed in colorectal carcinoma cells may kill the Fas-positive immune effective TILs by means of a Fas-FasL system termed Fas counterattack. 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subjects Adult
Aged
Aged, 80 and over
Apoptosis - physiology
Biological and medical sciences
Colorectal Neoplasms - immunology
Colorectal Neoplasms - pathology
DNA Fragmentation
Fas Ligand Protein
fas Receptor - biosynthesis
fas Receptor - immunology
Female
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Immunohistochemistry
Lymphocytes, Tumor-Infiltrating - cytology
Lymphocytes, Tumor-Infiltrating - immunology
Male
Medical sciences
Membrane Glycoproteins - biosynthesis
Membrane Glycoproteins - immunology
Middle Aged
Prognosis
Staining and Labeling - methods
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Tumors
title Frequency of Apoptosis of Tumor-infiltrating Lymphocytes Induced by Fas Counterattack in Human Colorectal Carcinoma and Its Correlation with Prognosis
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