A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_session3nmc2ojucvgqs0k6a1j6b7lkb3nqpdd8): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests

Filename: helpers/my_audit_helper.php

Line Number: 143

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 994
Function: getPubMedXML

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3134
Function: GetPubMedArticleOutput_2016

File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

Immunosuppressive CD29 Treg accumulation in the liver in mice on checkpoint inhibitor therapy. | LitMetric

AI Article Synopsis

  • Liver metastases often resist immune checkpoint inhibitor (ICI) therapy, and regulatory T cells (Tregs) in the liver may contribute to this resistance, but their specific role is not well understood.* -
  • The study utilized flow cytometry and RNA sequencing to analyze the behavior of hepatic Tregs, revealing a unique population that grows significantly in response to ICI treatment, regardless of tumor presence.* -
  • The findings suggest that a specific subpopulation of CD29 Tregs in the liver is crucial for the enhanced suppression and resistance to ICI therapy, indicating their potential as targets for improving treatment outcomes.*

Article Abstract

Objective: Liver metastases are often resistant to immune checkpoint inhibitor therapy (ICI) and portend a worse prognosis compared with metastases to other locations. Regulatory T cells (Tregs) are one of several immunosuppressive cells implicated in ICI resistance of liver tumours, but the role played by Tregs residing within the liver surrounding a tumour is unknown.

Design: Flow cytometry and single-cell RNA sequencing were used to characterise hepatic Tregs before and after ICI therapy.

Results: We found that the murine liver houses a Treg population that, unlike those found in other organs, is both highly proliferative and apoptotic at baseline. On administration of αPD-1, αPD-L1 or αCTLA4, the liver Treg population doubled regardless of the presence of an intrahepatic tumour. Remarkably, this change was not due to the preferential expansion of the subpopulation of Tregs that express PD-1. Instead, a subpopulation of CD29 (, integrin β1) Tregs, that were highly proliferative at baseline, doubled its size in response to αPD-1. Partial and full depletion of Tregs identified CD29 Tregs as the prominent niche-filling subpopulation in the liver, and CD29 Tregs demonstrated enhanced suppression when derived from the liver but not the spleen. We identified IL2 as a critical modulator of both CD29 and CD29 hepatic Tregs, but expansion of the liver Treg population with αPD-1 driven by CD29 Tregs was in part IL2-independent.

Conclusion: We propose that CD29 Tregs constitute a unique subpopulation of hepatic Tregs that are primed to respond to ICI agents and mediate resistance.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10922517PMC
http://dx.doi.org/10.1136/gutjnl-2023-330024DOI Listing

Publication Analysis

Top Keywords

cd29 tregs
16
tregs
12
hepatic tregs
12
treg population
12
liver
9
checkpoint inhibitor
8
inhibitor therapy
8
highly proliferative
8
liver treg
8
cd29
7

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!