Evidence map›Paper›PMID 36352891›Full record

ArticleOncoimmunology2022

Differential expression of CCR8 in tumors versus normal tissue allows specific depletion of tumor-infiltrating T regulatory cells by GS-1811, a novel Fc-optimized anti-CCR8 antibody.

Jessica D Weaver, Edward C Stack, Joshua A Buggé, Changyun Hu, Lara McGrath, Amy Mueller, Masie Wong, Boris Klebanov, Tanzila Rahman, Rosemary Kaufman and 19 more

Open access · goldAbstract read
In one paragraph

Article in Oncoimmunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
4.4field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 54 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Intratumoral TScience immunology · 2026
    Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors at 3 institutions in 3 countries.

Jessica D WeaverJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Edward C StackJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Joshua A BuggéJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Changyun HuJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Lara McGrathJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Amy MuellerJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Masie WongJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Boris KlebanovJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Tanzila RahmanJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Rosemary KaufmanJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Christine FregeauJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Vikki SpauldingJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Michelle PriessJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Kristen LegendreJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Sarah JaffeJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Dhruvkumar UpadhyayJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Anirudh SinghJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Chang-Ai XuJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Kristin KrukenbergJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Yan ZhangJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Yassine EzzyatJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Dorothée Saddier AxeGilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA.
Michelle R KuhneGilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA.
Michael A MeehlJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Donald R ShafferJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Brian M WeistGilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA.
Dmitri WiederschainJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Fabien DepisJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Monica GostissaJounce Therapeutics, Inc., 780 Memorial Drive, Cambridge, MA 02139, USA.
Memorial · RUGilead Sciences (United States) · USLakeside Labs · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The presence of T regulatory (Treg) cells in the tumor microenvironment is associated with poor prognosis and resistance to therapies aimed at reactivating anti-tumor immune responses. Therefore, depletion of tumor-infiltrating Tregs is a potential approach to overcome resistance to immunotherapy. However, identifying Treg-specific targets to drive such selective depletion is challenging. CCR8 has recently emerged as one of these potential targets. Here, we describe GS-1811, a novel therapeutic monoclonal antibody that specifically binds to human CCR8 and is designed to selectively deplete tumor-infiltrating Tregs. We validate previous findings showing restricted expression of CCR8 on tumor Tregs, and precisely quantify CCR8 receptor densities on tumor and normal tissue T cell subsets, demonstrating a window for selective depletion of Tregs in the tumor. Importantly, we show that GS-1811 depleting activity is limited to cells expressing CCR8 at levels comparable to tumor-infiltrating Tregs. Targeting CCR8 in mouse tumor models results in robust anti-tumor efficacy, which is dependent on Treg depleting activity, and synergizes with PD-1 inhibition to promote anti-tumor responses in PD-1 resistant models. Our data support clinical development of GS-1811 to target CCR8 in cancer and drive tumor Treg depletion in order to promote anti-tumor immunity.

Indexed as

NeoplasmsT-Lymphocytes, RegulatoryAnimalsHumansImmunoglobulin Fc FragmentsImmunotherapyMiceProgrammed Cell Death 1 ReceptorReceptors, CCR8Tumor MicroenvironmentCCR8 protein, humanCcr8 protein, mouseImmunoglobulin Fc FragmentsProgrammed Cell Death 1 ReceptorReceptors, CCR8cancer immunotherapyCCR8PD-1 resistancetreg depletionT regulatory cells

Identifiers

PMID36352891
PMCPMC9639568
OpenAlexW4308269714

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.