Evidence map›Paper›PMID 34215851›Full record

ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2021

Spatial immunoprofiling of the intratumoral and peritumoral tissue of renal cell carcinoma patients.

Oscar Brück, Moon Hee Lee, Riku Turkki, Ilona Uski, Patrick Penttilä, Lassi Paavolainen, Panu Kovanen, Petrus Järvinen, Petri Bono, Teijo Pellinen and 2 more

Abstract read
In one paragraph

Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–field-weighted citation impact
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

26 citing papers in PubMed.

  1. Loss of ARID1A expression is associated with worse survival and reduced tumor infiltrating lymphocytes in advanced clear cell renal cell carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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  11. Management of Renal Cell Carcinoma: Promising Biomarkers and the Challenges to Reach the Clinic.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Review
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  20. Clinical Impact of Immune Cells and Their Spatial Interactions in Diffuse Large B-Cell Lymphoma Microenvironment.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    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

12 authors.

Oscar BrückTranslational Immunology Research Program, University of Helsinki, Helsinki, Finland. oscar.bruck@hus.fi.ORCID 0000-0002-7842-9419
Moon Hee Lee *Translational Immunology Research Program, University of Helsinki, Helsinki, Finland.
Riku Turkki *Institute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-8690-6983
Ilona UskiTranslational Immunology Research Program, University of Helsinki, Helsinki, Finland.
Patrick PenttiläAbdominal Center, Urology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Lassi PaavolainenInstitute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Helsinki, Finland.ORCID 0000-0003-1508-2718
Panu KovanenDepartment of Pathology, HUSLAB, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Petrus JärvinenAbdominal Center, Urology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Petri BonoComprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.ORCID 0000-0003-3963-0416
Teijo PellinenInstitute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Helsinki, Finland.ORCID 0000-0001-9652-7373
Satu Mustjoki *Translational Immunology Research Program, University of Helsinki, Helsinki, Finland. satu.mustjoki@helsinki.fi.ORCID 0000-0002-0816-8241
Anna Kreutzman *Translational Immunology Research Program, University of Helsinki, Helsinki, Finland. anna.kreutzman@helsinki.fi.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

While the abundance and phenotype of tumor-infiltrating lymphocytes are linked with clinical survival, their spatial coordination and its clinical significance remain unclear. Here, we investigated the immune profile of intratumoral and peritumoral tissue of clear cell renal cell carcinoma patients (n = 64). We trained a cell classifier to detect lymphocytes from hematoxylin and eosin stained tissue slides. Using unsupervised classification, patients were further classified into immune cold, hot and excluded topographies reflecting lymphocyte abundance and localization. The immune topography distribution was further validated with The Cancer Genome Atlas digital image dataset. We showed association between PBRM1 mutation and immune cold topography, STAG1 mutation and immune hot topography and BAP1 mutation and immune excluded topography. With quantitative multiplex immunohistochemistry we analyzed the expression of 23 lymphocyte markers in intratumoral and peritumoral tissue regions. To study spatial interactions, we developed an algorithm quantifying the proportion of adjacent immune cell pairs and their immunophenotypes. Immune excluded tumors were associated with superior overall survival (HR 0.19, p = 0.02) and less extensive metastasis. Intratumoral T cells were characterized with pronounced expression of immunological activation and exhaustion markers such as granzyme B, PD1, and LAG3. Immune cell interaction occurred most frequently in the intratumoral region and correlated with CD45RO expression. Moreover, high proportion of peritumoral CD45RO+ T cells predicted poor overall survival. In summary, intratumoral and peritumoral tissue regions represent distinct immunospatial profiles and are associated with clinicopathologic characteristics.

Indexed as

AlgorithmsDecision Support TechniquesImmunohistochemistryImmunophenotypingAdultAgedAged, 80 and overBiomarkers, TumorCarcinoma, Renal CellDNA-Binding ProteinsFemaleHumansKidney NeoplasmsLeukocyte Common AntigensLymphocytes, Tumor-InfiltratingMaleBAP1 protein, humanBiomarkers, TumorDNA-Binding ProteinsLeukocyte Common AntigensNuclear ProteinsPBRM1 protein, humanSTAG1 protein, humanTranscription FactorsTumor Suppressor ProteinsUbiquitin Thiolesterase

Identifiers

PMID34215851
PMCPMC8592837

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.