Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Active Surveillance Characterizes Human Intratumoral T Cell Exhaustion

Ran You, Jordan Artichoker, Adam Fries, Austin Edwards, Alexis Combes, Gabriella Reeder, Bushra Samad, View ORCID ProfileMatthew F. Krummel
doi: https://doi.org/10.1101/2021.05.06.443033
Ran You
1Department of Pathology, University of California San Francisco
2ImmunoX Initiative, University of California San Francisco
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jordan Artichoker
2ImmunoX Initiative, University of California San Francisco
3Biological Imaging Development CoLab, University of California San Francisco
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Adam Fries
2ImmunoX Initiative, University of California San Francisco
3Biological Imaging Development CoLab, University of California San Francisco
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Austin Edwards
2ImmunoX Initiative, University of California San Francisco
3Biological Imaging Development CoLab, University of California San Francisco
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexis Combes
2ImmunoX Initiative, University of California San Francisco
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gabriella Reeder
2ImmunoX Initiative, University of California San Francisco
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bushra Samad
2ImmunoX Initiative, University of California San Francisco
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthew F. Krummel
1Department of Pathology, University of California San Francisco
2ImmunoX Initiative, University of California San Francisco
3Biological Imaging Development CoLab, University of California San Francisco
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Matthew F. Krummel
  • For correspondence: matthew.krummel@ucsf.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Intratumoral T cells that might otherwise control tumors are often identified in an ‘exhausted’ state, defined by specific epigenetic modifications as well as upregulation of genes such as CD38, CTLA-4 and PD-1. While the term might imply inactivity, there has been little study of this state at the phenotypic level in tumors to understand the extent of their incapacitation. Starting with the observation that T cells move more quickly through mouse tumors as residence time increases and they progress towards exhaustion, we elaborated a non-stimulatory live-biopsy method for real-time study of T cell behaviors within individual patient tumors. Using two-photon microscopy, we studied native CD8 T cells interacting with APCs and with cancer cells in different micro-niches of human tumors, finding that T cell speed was variable by region and by patient, was independent of T cell density and was inversely correlated with local tumor density. Across a range of tumor types, we found a strong relationship between CD8 T cell motility and exhausted T cell state that corresponds to observations made in mouse models where exhausted T cells move faster. While this is a small study, it demonstrates at least two types of T cell dynamic states in individual human tumors and supports the existence of an active program in ‘exhausted’ T cells that extends beyond incapacitating them.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted May 07, 2021.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Active Surveillance Characterizes Human Intratumoral T Cell Exhaustion
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Active Surveillance Characterizes Human Intratumoral T Cell Exhaustion
Ran You, Jordan Artichoker, Adam Fries, Austin Edwards, Alexis Combes, Gabriella Reeder, Bushra Samad, Matthew F. Krummel
bioRxiv 2021.05.06.443033; doi: https://doi.org/10.1101/2021.05.06.443033
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Active Surveillance Characterizes Human Intratumoral T Cell Exhaustion
Ran You, Jordan Artichoker, Adam Fries, Austin Edwards, Alexis Combes, Gabriella Reeder, Bushra Samad, Matthew F. Krummel
bioRxiv 2021.05.06.443033; doi: https://doi.org/10.1101/2021.05.06.443033

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Immunology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3607)
  • Biochemistry (7581)
  • Bioengineering (5529)
  • Bioinformatics (20809)
  • Biophysics (10338)
  • Cancer Biology (7988)
  • Cell Biology (11647)
  • Clinical Trials (138)
  • Developmental Biology (6611)
  • Ecology (10217)
  • Epidemiology (2065)
  • Evolutionary Biology (13630)
  • Genetics (9550)
  • Genomics (12854)
  • Immunology (7925)
  • Microbiology (19555)
  • Molecular Biology (7668)
  • Neuroscience (42147)
  • Paleontology (308)
  • Pathology (1258)
  • Pharmacology and Toxicology (2203)
  • Physiology (3269)
  • Plant Biology (7051)
  • Scientific Communication and Education (1294)
  • Synthetic Biology (1952)
  • Systems Biology (5429)
  • Zoology (1119)