Evidence map›Paper›PMID 29033936›Full record

ReviewFrontiers in immunology2017

Coinhibitory Receptor Expression and Immune Checkpoint Blockade: Maintaining a Balance in CD8

Isobel S Okoye, Michael Houghton, Lorne Tyrrell, Khaled Barakat, Shokrollah Elahi

Open access · goldAbstract readReview
In one paragraph

Review in Frontiers in immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed, 1 pooled it
4.7field-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

68 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.

  1. Pooled it
  2. Immune checkpoint molecules beyond PD-1 and CTLA-4: emerging targets in autoimmune diseases and cancer immunotherapy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  3. Article
  4. Article
  5. Triple checkpoint blockade of PD-1, Tim-3, and Lag-3 enhances adoptive T cell immunotherapy in a mouse model of ovarian cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  6. Polyfunctional CD8Molecular oncology · 2025
    Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Immunological responses in SARS-CoV-2 and HIV co-infection versus SARS-CoV-2 mono-infection: case report of the interplay between SARS-CoV-2 and HIV.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2023
    Article
  16. Double Positive CD4Cells · 2023
    Article
  17. CD71Journal for immunotherapy of cancer · 2023
    Article
  18. Review
  19. Depletion of polyfunctional CD26Experimental hematology & oncology · 2023
    Article
  20. Article

8 more citing papers are in PubMed but not listed here.

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

5 authors at 1 institution in 1 country.

Isobel S OkoyeDepartment of Dentistry, University of Alberta, Edmonton, AB, Canada.
Michael HoughtonDepartment of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada.
Lorne TyrrellDepartment of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada.
Khaled BarakatFaculty of Medicine and Dentistry, Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB, Canada.
Shokrollah ElahiDepartment of Dentistry, University of Alberta, Edmonton, AB, Canada.
University of Alberta · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In cancer and chronic viral infections, T cells are exposed to persistent antigen stimulation. This results in expression of multiple inhibitory receptors also called "immune checkpoints" by T cells. Although these inhibitory receptors under normal conditions maintain self-tolerance and prevent immunopathology, their sustained expression deteriorates T cell function: a phenomenon called exhaustion. Recent advances in cancer immunotherapy involve blockade of cytotoxic T lymphocyte antigen-4 and programmed cell death 1 in order to reverse T cell exhaustion and reinvigorate immunity, which has translated to dramatic clinical remission in many cases of metastatic melanoma and lung cancer. With the paucity of therapeutic vaccines against chronic infections such as HIV, HPV, hepatitis B, and hepatitis C, such adjunct checkpoint blockade strategies are required including the blockade of other inhibitory receptors such as T cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif domains, T cell Ig and mucin-domain containing-3, lymphocyte activation gene 3, and V-domain Ig-containing suppressor of T cell activation. The nature of different chronic viral infections and cancers is likely to influence the level, composition, and pattern of inhibitory receptors expressed by responding T cells. This will have implications for checkpoint antibody blockade strategies employed for treating tumors and chronic viral infections. Here, we review recent advances that provide a clearer insight into the role of coinhibitory receptor expression in T cell exhaustion and reveal novel antibody-blockade therapeutic targets for chronic viral infections and cancer. Understanding the mechanism of T cell exhaustion in response to chronic virus infections and cancer as well as the nature of restored T cell responses will contribute to further improvement of immune checkpoint blockade strategies.

Indexed as

cancercheckpoint blockadechronic infectionsimmune checkpointsimmunotherapyT cell exhaustion

Identifiers

PMID29033936
PMCPMC5626929
OpenAlexW2760003250

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.