Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1391840
This article is part of the Research Topic Peripheral Blood-Based Biomarkers for Immune Monitoring of Cancer and Cancer Therapy View all 19 articles

Peripheral Immune Profiling of Soft Tissue Sarcoma: Perspectives for Disease Monitoring

Provisionally accepted
Jani Almeida Jani Almeida 1Luana Sousa Luana Sousa 1Patrícia Couceiro Patrícia Couceiro 1Tania C. Andrade Tania C. Andrade 1Vera Alves Vera Alves 1Antonio Martinho Antonio Martinho 2Joana Rodrigues Joana Rodrigues 3Ruben Fonseca Ruben Fonseca 3Paulo F. Tavares Paulo F. Tavares 3Manuel Santos-Rosa Manuel Santos-Rosa 1José Manuel Casanova José Manuel Casanova 3Paulo Rodrigues-Santos Paulo Rodrigues-Santos 4*
  • 1 University of Coimbra, Coimbra, Coimbra, Portugal
  • 2 Portuguese Institute of Blood and Transplantation (IPST), Lisbon, Portugal
  • 3 Coimbra Hospital and University Center, Coimbra, Coimbra, Portugal
  • 4 Instituto de Imunologia, Immunology and Oncology Laboratory, Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

The final, formatted version of the article will be published soon.

    Studying the tumor microenvironment and surrounding lymph nodes is the main focus of current immunological research on soft tissue sarcomas (STS). However, due to the restricted opportunity to examine tumor samples, alternative approaches are required to evaluate immune responses in non-surgical patients. Therefore, the purpose of this study was to evaluate the peripheral immune profile of STS patients, characterize patients accordingly and explore the impact of peripheral immunotypes on patient survival. Blood samples were collected from 55 STS patients and age-matched healthy donors (HD) controls. Deep immunophenotyping and gene expression analysis of whole blood was analyzed using multiparametric flow cytometry and real-time RT-qPCR, respectively. Using xMAP technology, proteomic analysis was also carried out on plasma samples. Unsupervised clustering analysis was used to classify patients based on their immune profiles to further analyze the impact of peripheral immunotypes on patient survival. Significant differences were found between STS patients and HD controls. It was found a contraction of B cells and CD4 T cells compartment, along with decreased expression levels of ICOSLG and CD40LG; a major contribution of suppressor factors, as increased frequency of M-MDSC and memory Tregs, increased expression levels of ARG1, and increased plasma levels of IL-10, soluble VISTA and soluble TIMD-4; and a compromised cytotoxic potential associated with NK and CD8 T cells, namely decreased frequency of CD56 dim NK cells, and decreased levels of PRF1, GZMB, and KLRK1. In addition, the patients were classified into three peripheral immunotype groups: "immune-high," "immuneintermediate," and "immune-low." Furthermore, it was found a correlation between these immunotypes and patient survival. Patients classified as "immune-high" exhibited higher levels of immune-related factors linked to cytotoxic/effector activity and longer survival times, whereas patients classified as "immune-low" displayed higher levels of immune factors associated with immunosuppression and shorter survival times. In conclusion, it can be suggested that STS patients have a compromised systemic immunity, and the correlation between immunotypes and survival emphasizes the importance of studying peripheral blood samples in STS. Assessing the peripheral immune response holds promise as a useful method for monitoring and forecasting outcomes in STS.

    Keywords: Soft Tissue Sarcoma, Immunophenotyping, Gene Expression Profiling, Cytokines, Chemokines, growth factors, immune checkpoints, overall survival Justified

    Received: 26 Feb 2024; Accepted: 30 Sep 2024.

    Copyright: © 2024 Almeida, Sousa, Couceiro, Andrade, Alves, Martinho, Rodrigues, Fonseca, Tavares, Santos-Rosa, Casanova and Rodrigues-Santos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Paulo Rodrigues-Santos, Instituto de Imunologia, Immunology and Oncology Laboratory, Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3004-504, Portugal

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.