Initiation of inflammatory tumorigenesis by CTLA4 insufficiency due to type 2 cytokines
Miska, J., Lui, J. B., Toomer, K. H., Devarajan, P., Cai, X., Houghton, J., Lopez, D. M., Abreu, M. T., Wang, G., Chen, Z.
Rockefeller University Press
Published 2018
Rockefeller University Press
Published 2018
| Publication Date: |
2018-03-06
|
|---|---|
| Publisher: |
Rockefeller University Press
|
| Print ISSN: |
0022-1007
|
| Electronic ISSN: |
1540-9538
|
| Topics: |
Medicine
|
| Keywords: |
Autoimmunity, Tumor Immunology
|
| Published by: |
| _version_ | 1836398824664334336 |
|---|---|
| autor | Miska, J., Lui, J. B., Toomer, K. H., Devarajan, P., Cai, X., Houghton, J., Lopez, D. M., Abreu, M. T., Wang, G., Chen, Z. |
| beschreibung | Genetically predisposed CTLA4 insufficiency in humans is associated with gastric cancer development, which is paradoxical to the prototypical role of CTLA4 in suppressing antitumor immunity. CTLA4 is a critical immune checkpoint against autoimmune disorders. Autoimmunity has been implicated in protumor or antitumor activities. Here, we show that CTLA4 insufficiency initiates de novo tumorigenesis in the mouse stomach through inflammation triggered by host-intrinsic immune dysregulation rather than microbiota, with age-associated progression to malignancy accompanied by epigenetic dysregulation. The inflammatory tumorigenesis required CD4 T cells, but not the T H 1 or T H 17 subsets. Deficiencies in IL-4 and IL-13 or IL-4 receptor α broke the link between inflammation and initiation of tumorigenesis. This study establishes the causality of CTLA4 insufficiency in gastric cancer and uncovers a role of type 2 inflammation in initiating gastric epithelial transformation. These findings suggest possible improvement of immune therapies by blocking tumorigenic type 2 inflammation while preserving antitumor type 1 immunity. |
| citation_standardnr | 6189219 |
| datenlieferant | ipn_articles |
| feed_id | 96 |
| feed_publisher | Rockefeller University Press |
| feed_publisher_url | http://www.rupress.org/ |
| insertion_date | 2018-03-06 |
| journaleissn | 1540-9538 |
| journalissn | 0022-1007 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | Rockefeller University Press |
| quelle | Journal of Experimental Medicine |
| relation | http://jem.rupress.org/cgi/content/short/215/3/841?rss=1 |
| schlagwort | Autoimmunity, Tumor Immunology |
| search_space | articles |
| shingle_author_1 | Miska, J., Lui, J. B., Toomer, K. H., Devarajan, P., Cai, X., Houghton, J., Lopez, D. M., Abreu, M. T., Wang, G., Chen, Z. |
| shingle_author_2 | Miska, J., Lui, J. B., Toomer, K. H., Devarajan, P., Cai, X., Houghton, J., Lopez, D. M., Abreu, M. T., Wang, G., Chen, Z. |
| shingle_author_3 | Miska, J., Lui, J. B., Toomer, K. H., Devarajan, P., Cai, X., Houghton, J., Lopez, D. M., Abreu, M. T., Wang, G., Chen, Z. |
| shingle_author_4 | Miska, J., Lui, J. B., Toomer, K. H., Devarajan, P., Cai, X., Houghton, J., Lopez, D. M., Abreu, M. T., Wang, G., Chen, Z. |
| shingle_catch_all_1 | Initiation of inflammatory tumorigenesis by CTLA4 insufficiency due to type 2 cytokines Autoimmunity, Tumor Immunology Genetically predisposed CTLA4 insufficiency in humans is associated with gastric cancer development, which is paradoxical to the prototypical role of CTLA4 in suppressing antitumor immunity. CTLA4 is a critical immune checkpoint against autoimmune disorders. Autoimmunity has been implicated in protumor or antitumor activities. Here, we show that CTLA4 insufficiency initiates de novo tumorigenesis in the mouse stomach through inflammation triggered by host-intrinsic immune dysregulation rather than microbiota, with age-associated progression to malignancy accompanied by epigenetic dysregulation. The inflammatory tumorigenesis required CD4 T cells, but not the T H 1 or T H 17 subsets. Deficiencies in IL-4 and IL-13 or IL-4 receptor α broke the link between inflammation and initiation of tumorigenesis. This study establishes the causality of CTLA4 insufficiency in gastric cancer and uncovers a role of type 2 inflammation in initiating gastric epithelial transformation. These findings suggest possible improvement of immune therapies by blocking tumorigenic type 2 inflammation while preserving antitumor type 1 immunity. Miska, J., Lui, J. B., Toomer, K. H., Devarajan, P., Cai, X., Houghton, J., Lopez, D. M., Abreu, M. T., Wang, G., Chen, Z. Rockefeller University Press 0022-1007 00221007 1540-9538 15409538 |
| shingle_catch_all_2 | Initiation of inflammatory tumorigenesis by CTLA4 insufficiency due to type 2 cytokines Autoimmunity, Tumor Immunology Genetically predisposed CTLA4 insufficiency in humans is associated with gastric cancer development, which is paradoxical to the prototypical role of CTLA4 in suppressing antitumor immunity. CTLA4 is a critical immune checkpoint against autoimmune disorders. Autoimmunity has been implicated in protumor or antitumor activities. Here, we show that CTLA4 insufficiency initiates de novo tumorigenesis in the mouse stomach through inflammation triggered by host-intrinsic immune dysregulation rather than microbiota, with age-associated progression to malignancy accompanied by epigenetic dysregulation. The inflammatory tumorigenesis required CD4 T cells, but not the T H 1 or T H 17 subsets. Deficiencies in IL-4 and IL-13 or IL-4 receptor α broke the link between inflammation and initiation of tumorigenesis. This study establishes the causality of CTLA4 insufficiency in gastric cancer and uncovers a role of type 2 inflammation in initiating gastric epithelial transformation. These findings suggest possible improvement of immune therapies by blocking tumorigenic type 2 inflammation while preserving antitumor type 1 immunity. Miska, J., Lui, J. B., Toomer, K. H., Devarajan, P., Cai, X., Houghton, J., Lopez, D. M., Abreu, M. T., Wang, G., Chen, Z. Rockefeller University Press 0022-1007 00221007 1540-9538 15409538 |
| shingle_catch_all_3 | Initiation of inflammatory tumorigenesis by CTLA4 insufficiency due to type 2 cytokines Autoimmunity, Tumor Immunology Genetically predisposed CTLA4 insufficiency in humans is associated with gastric cancer development, which is paradoxical to the prototypical role of CTLA4 in suppressing antitumor immunity. CTLA4 is a critical immune checkpoint against autoimmune disorders. Autoimmunity has been implicated in protumor or antitumor activities. Here, we show that CTLA4 insufficiency initiates de novo tumorigenesis in the mouse stomach through inflammation triggered by host-intrinsic immune dysregulation rather than microbiota, with age-associated progression to malignancy accompanied by epigenetic dysregulation. The inflammatory tumorigenesis required CD4 T cells, but not the T H 1 or T H 17 subsets. Deficiencies in IL-4 and IL-13 or IL-4 receptor α broke the link between inflammation and initiation of tumorigenesis. This study establishes the causality of CTLA4 insufficiency in gastric cancer and uncovers a role of type 2 inflammation in initiating gastric epithelial transformation. These findings suggest possible improvement of immune therapies by blocking tumorigenic type 2 inflammation while preserving antitumor type 1 immunity. Miska, J., Lui, J. B., Toomer, K. H., Devarajan, P., Cai, X., Houghton, J., Lopez, D. M., Abreu, M. T., Wang, G., Chen, Z. Rockefeller University Press 0022-1007 00221007 1540-9538 15409538 |
| shingle_catch_all_4 | Initiation of inflammatory tumorigenesis by CTLA4 insufficiency due to type 2 cytokines Autoimmunity, Tumor Immunology Genetically predisposed CTLA4 insufficiency in humans is associated with gastric cancer development, which is paradoxical to the prototypical role of CTLA4 in suppressing antitumor immunity. CTLA4 is a critical immune checkpoint against autoimmune disorders. Autoimmunity has been implicated in protumor or antitumor activities. Here, we show that CTLA4 insufficiency initiates de novo tumorigenesis in the mouse stomach through inflammation triggered by host-intrinsic immune dysregulation rather than microbiota, with age-associated progression to malignancy accompanied by epigenetic dysregulation. The inflammatory tumorigenesis required CD4 T cells, but not the T H 1 or T H 17 subsets. Deficiencies in IL-4 and IL-13 or IL-4 receptor α broke the link between inflammation and initiation of tumorigenesis. This study establishes the causality of CTLA4 insufficiency in gastric cancer and uncovers a role of type 2 inflammation in initiating gastric epithelial transformation. These findings suggest possible improvement of immune therapies by blocking tumorigenic type 2 inflammation while preserving antitumor type 1 immunity. Miska, J., Lui, J. B., Toomer, K. H., Devarajan, P., Cai, X., Houghton, J., Lopez, D. M., Abreu, M. T., Wang, G., Chen, Z. Rockefeller University Press 0022-1007 00221007 1540-9538 15409538 |
| shingle_title_1 | Initiation of inflammatory tumorigenesis by CTLA4 insufficiency due to type 2 cytokines |
| shingle_title_2 | Initiation of inflammatory tumorigenesis by CTLA4 insufficiency due to type 2 cytokines |
| shingle_title_3 | Initiation of inflammatory tumorigenesis by CTLA4 insufficiency due to type 2 cytokines |
| shingle_title_4 | Initiation of inflammatory tumorigenesis by CTLA4 insufficiency due to type 2 cytokines |
| timestamp | 2025-06-30T23:33:13.675Z |
| titel | Initiation of inflammatory tumorigenesis by CTLA4 insufficiency due to type 2 cytokines |
| titel_suche | Initiation of inflammatory tumorigenesis by CTLA4 insufficiency due to type 2 cytokines |
| topic | WW-YZ |
| uid | ipn_articles_6189219 |