Evidence map›Paper›PMID 33035322›Full record

ArticleCarcinogenesis2020

Digitally quantified CD8+ cells: the best candidate marker for an immune cell score in non-small cell lung cancer?

Thomas K Kilvaer, Erna-Elise Paulsen, Sigve Andersen, Mehrdad Rakaee, Roy M Bremnes, Lill-Tove Rasmussen Busund, Tom Donnem

Open access · bronzeAbstract read
In one paragraph

Article in Carcinogenesis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 9% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. CD3Scientific reports · 2026
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  12. Rethinking the role of biomarkers for operable non-small cell lung carcinoma: an effective collaboration with artificial intelligence algorithms.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022
    Article
  13. The effect of neoadjuvant therapy on PD-L1 expression and CD8+lymphocyte density in non-small cell lung cancer.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022
    Article
  14. Article
  15. Article
  16. Article
  17. CD8Frontiers in immunology · 2022
    Article
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  19. Review
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

7 authors at 2 institutions in 1 country.

Thomas K KilvaerDepartment of Oncology, University Hospital of North Norway, Tromso, Norway.
Erna-Elise PaulsenDepartment of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.
Sigve AndersenDepartment of Oncology, University Hospital of North Norway, Tromso, Norway.
Mehrdad RakaeeDepartment of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.
Roy M BremnesDepartment of Oncology, University Hospital of North Norway, Tromso, Norway.
Lill-Tove Rasmussen BusundDepartment of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway.
Tom DonnemDepartment of Oncology, University Hospital of North Norway, Tromso, Norway.
University Hospital of North Norway · NOUiT The Arctic University of Norway · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The TNM classification is well established as a state-of-the-art prognostic and treatment-decision-making tool for non-small cell lung cancer (NSCLC) patients. However, incorporation of biological data may hone the TNM system. This article focuses on choosing and incorporating subsets of tissue-infiltrating lymphocyte (TIL), detected by specific immunohistochemistry and automatically quantified by open source software, into a TNM-Immune cell score (TNM-I) for NSCLC. We use common markers (CD3, CD4, CD8, CD20 and CD45RO) of TILs to identify TIL subsets in tissue micro-arrays comprising tumor tissue from 553 patients resected for primary NSCLC. The number of TILs is automatically quantified using open source software (QuPath). Their prognostic efficacy, alone and within a TNM-I model, is evaluated in all patients and histological subgroups. Compared with previous manual semi-quantitative scoring of TILs in the same cohort, the present digital quantification proved superior. As a proof-of-concept, we construct a TNM-I, using TNM categories and the CD8+ TIL density. The TNM-I is an independent prognosticator of favorable diagnosis in both the overall cohort and in the main histological subgroups. In conclusion, CD8+ TIL density is the most promising candidate marker for a TNM-I in NSCLC. The prognostic efficacy of the CD8+ TIL density is strongest in lung squamous cell carcinomas, whereas both CD8+ TILs and CD20+ TILs, or a combination of these, may be candidates for a TNM-I in lung adenocarcinoma. Furthermore, based on the presented results, digital quantification is the preferred method for scoring TILs in the future.

Indexed as

Adenocarcinoma of LungAgedBiomarkers, TumorCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellCD8-Positive T-LymphocytesFemaleFollow-Up StudiesHumansLung NeoplasmsLymphocytes, Tumor-InfiltratingMaleNeoplasm StagingRetrospective StudiesSurvival RateTumor Cells, CulturedBiomarkers, Tumor

Identifiers

PMID33035322
PMCPMC7791621
OpenAlexW3091897809

What OpenQuestion holds

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Registered trials

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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.