Evidence map›Paper›PMID 34885185›Full record

ArticleCancers2021

Tumor-Infiltrating Lymphocytes and Cancer Markers in Osteosarcoma: Influence on Patient Survival.

José Manuel Casanova, Jani-Sofia Almeida, John David Reith, Luana Madalena Sousa, Ruben Fonseca, Paulo Freitas-Tavares, Manuel Santos-Rosa, Paulo Rodrigues-Santos

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.5field-weighted citation impact, top 6% 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

30 citing papers in PubMed, 36 citations in OpenAlex.

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  6. A comprehensive clinico-pathological review of a series of pediatric, adolescents and young adults with high-grade osteosarcoma: from clinics to biomarker discovery.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
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  8. Involvement ofFrontiers in oncology · 2025
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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

8 authors at 3 institutions in 2 countries.

José Manuel CasanovaTumor Unit of the Locomotor Apparatus (UTAL), University Clinic of Orthopedics, Orthopedics Service, Coimbra Hospital and Universitary Centre (CHUC), 3000-075 Coimbra, Portugal.ORCID 0000-0002-0561-0364
Jani-Sofia AlmeidaCenter of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.
John David ReithDepartment of Pathology, Robert J. Tomsich Pathology & Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Luana Madalena SousaLaboratory of Immunology and Oncology, Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-504 Coimbra, Portugal.
Ruben FonsecaTumor Unit of the Locomotor Apparatus (UTAL), University Clinic of Orthopedics, Orthopedics Service, Coimbra Hospital and Universitary Centre (CHUC), 3000-075 Coimbra, Portugal.
Paulo Freitas-TavaresTumor Unit of the Locomotor Apparatus (UTAL), University Clinic of Orthopedics, Orthopedics Service, Coimbra Hospital and Universitary Centre (CHUC), 3000-075 Coimbra, Portugal.ORCID 0000-0001-7832-4134
Manuel Santos-RosaCenter of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.
Paulo Rodrigues-SantosCenter of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.ORCID 0000-0001-7519-1620
Escola Superior de Tecnologia da Saúde de Coimbra · PTCleveland Clinic · USUniversity of Coimbra · PT

Funding

Fundação para a Ciência e Tecnologia POCI-01-0145-FEDER-007440Fundação para a Ciência e Tecnologia UIDB/04539/2020Fundação para a Ciência e Tecnologia UIDP/04539/2020
6 · The paper itself

Abstract

Osteosarcoma (OST) is the most common type of high-grade primary bone tumor, which mainly affects young adults. The current standard of care for OST combines surgical resection with chemotherapy. The clinical outcomes and the current options to treat OST patients are unsatisfactory and novel treatment strategies are needed. The crosstalk between tumor cells and immune cells is essential to the OST microenvironment. Despite the efforts that have been made to address the importance of immune-related factors in OST, there is still a lot to understand. The purpose of the current study was to evaluate the tumor-infiltrating lymphocytes (TIL), the expression of proteins involved in tumor biology, and their impact on the clinical outcome of OST patients. We studied 93 samples of OST patients using immunohistochemistry and histomorphometry. We looked for the infiltration of CD3+, CD4+, CD8+, TIA1+ and CD20+ cells and for the expression of CD44 standard (CD44s) and variant 6 (CD44v6), CD95/Fas, Fas-L, p53 and p-glycoprotein. All the parameters were analyzed for the influence on the occurrence of death and metastasis, plus patient overall survival (OS) and progression-free survival (PFS). The effect of sex, age, tumor location (distal femur or proximal tibia) and the combination with neoadjuvant chemotherapy was also assessed. Our results suggest that the presence of tumor-infiltrating CD4+ cells provides protection to OST patients, and that CD8+ cells have a significant impact on the patient's overall survival (OS) and progression-free survival (PFS), which is more evident in male patients. In addition, a strong association between tumor-infiltrating CD4+ cells and the presence of CD44s expression in tumor samples was observed. Analysis of TIL and tumor markers related to tumor biology could be useful to stratify patients and monitor the response to therapy, as well as to assist with the development of immunotherapy strategies to improve the effects of cytotoxic TIL to eradicate the tumor cells.

Indexed as

osteosarcomasurvivaltumor-infiltrating lymphocytestumor markerstumor microenvironment

Identifiers

PMID34885185
PMCPMC8656728
OpenAlexW3217628998

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.