Federica Recine1
Alberto Bongiovanni2
Laura Mercatali3
Valentina Fausti2
Virginia Ferraresi4
Alessandro De Vita5*- 1Medical Oncology Unit, Azienda Ospedaliera “San Giovanni Addolorata”, Roma, Italy
- 2Clinical and Experimental Oncology, Immunotherapy, Rare Cancers and Biological Resource Center, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
- 3Osteoncology, Bone and Soft Tissue Sarcomas and Innovative Therapies Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
- 4Sarcomas and Rare Tumors Unit, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Rome, Italy
- 5Preclinic and Osteoncology Unit, Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
Editorial on the Research Topic
The immune infiltrate as a paradigm model to study the biology and novel therapeutic approaches in sarcomas
The tumor immune microenvironment (TiME) plays an essential role in tumor development as well as in tumor metastatization in a plethora of neoplasms, including soft tissue sarcoma (STS) and bone sarcomas (1). STS and bone sarcomas are a heterogeneous group of solid malignancies, encompassing more than 100 histological subtypes, with different biological and clinical behaviors, genomic backgrounds, and responses to treatments (2–4).
TiME is a dynamic milieu of various types of elements, such as infiltrating immune cells, tumoral cells, and extracellular matrix, that have a potential role in the cancer growth process. Further understanding of the TiME mechanism is crucial for the development of new therapeutic agents, such as immunotherapy and its clinical application. Moreover, studying the role of the TiME in STS may contribute to improving the knowledge of the natural history and disease biology in this heterogenous group of rare mesenchymal tumors (5, 6).
Articles published as part of the Research Topic “The Immune Infiltrate as a Paradigm Model to Study the Biology and Novel Therapeutic Approaches in Sarcomas” highlight the recent discoveries in this field, emphasizing the crucial role of the TiME in the etiopathogenesis of STS with the correlated clinical implications.
Wu et al. explored the correlation between angiogenesis and the TiME in osteosarcoma (OS) that underlies the network between the vessel state and immune infiltrate in this neoplasm. In the study, two subgroups of OS patients were identified according to the expression of angiogenesis-related genes (ARGs), and the vessel state and TiME of these groups were compared. The ARG score showed the correlation with angiogenesis and characterized the immune landscape of OS, leading to a risk score model and a prediction model of OS in the prognosis and response to immunotherapy.
In this context, Liao et al. focused on the role of sulfatinib, a novel multi-targeted tyrosine kinase inhibitor (TKI), in the management of OS patients. This agent showed dual activity as a multi-target TKI that inhibits proliferation in OS cells, by phosphorylating FGFR1 and downstream kinases, and modulates the TiME, increasing chemotherapy sensitivity.
Furthermore, in bone sarcomas, Weil and Loeb provided a detailed overview of the bone tumor microenvironment with a description of the various potential cancer mechanisms in this interplay. The authors emphasized the role of the crosstalk between sarcomas and the bone microenvironment, contributing to the control of tumor growth and cell extravasation and metastasis, as well as the implicated therapeutic potential options.
Another sarcoma histotype in which there is a relationship between systemic immune activation, angiogenesis, and tumor pathogenesis is Kaposi’s sarcoma (KS). The authors reported a potential correlation between soluble markers of HIV-1-related immune activation and the level of growth factors in HHV-8 seropositive KS patients (Nana et al.).
The crucial role of TiME in tumorigenesis was also evaluated in epithelial tumors; in particular, in lung cancer, as described by (Zhao et al.). The authors hypothesized a correlation between the changes in serum cytokine levels and the effectiveness of targeted immunotherapy in lung cancer and suggested immunological biomarkers as prognostic predictors for lung cancer.
In conclusion, the role of the TiME in the pathogenesis of tumors is still being studied due to the complexity and heterogeneity of this highly dynamic network of various elements. In this context, targeting the tumor microenvironment may be a promising therapeutic strategy for reducing tumor growth and metastasis and blocking therapeutic resistance.
Author contributions
FR: Writing – original draft. AB: Writing – review & editing. LM: Writing – review & editing. VFa: Writing – review & editing. VFe: Writing – review & editing. ADV: Writing – review & editing.
Funding
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was partly supported thanks to the contribution of Ricerca Corrente by the Italian Ministry of Health.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s note
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.
References
1. Huang RZ, Meng T, Chen R, Yan P, Zhang J, Hu P, et al. The construction and analysis of tumor-infiltrating immune cell and ceRNA network in recurrent soft tissue sarcoma. Aging (2019) 11:10116–43. doi: 10.18632/aging.102424
2. Miettinen M, Felisiak-Golabek A, Luiña Contreras A, Glod J, Kaplan RN, Killian JK, et al. New fusion sarcomas: histopathology and clinical significance of selected entities. Hum Pathol (2019) 86:57–65. doi: 10.1016/j.humpath.2018.12.006
3. WHO Classification of Tumours Editorial Board. WHO Classification of Tumours of Soft Tissue and Bone. 5th ed. Lyon, France: IARC Press (2020).
4. Recine F, De Vita A, Fausti V, Pieri F, Bongiovanni A, Franchini E, et al. Case report: adult NTRK-rearranged spindle cell neoplasm: early tumor shrinkage in a case with bone and visceral metastases treated with targeted therapy. Front Oncol (2022) 11:740676. doi: 10.3389/fonc.2021.740676
5. De Vita A, Recine F, Miserocchi G, Pieri F, Spadazzi C, Cocchi C, et al. The potential role of the extracellular matrix in the activity of trabectedin in UPS and L-sarcoma: evidences from a patient-derived primary culture case series in tridimensional and zebrafish models. J Exp Clin Cancer Res (2021) 40(1):165. doi: 10.1186/s13046-021-01963-1
Keywords: sarcomas, immunotherapy, tumor microenvironment, extracellular matrix, macrophages, T-cell infiltration
Citation: Recine F, Bongiovanni A, Mercatali L, Fausti V, Ferraresi V and De Vita A (2023) Editorial: The immune infiltrate as a paradigm model to study the biology and novel therapeutic approaches in sarcomas. Front. Endocrinol. 14:1334519. doi: 10.3389/fendo.2023.1334519
Received: 07 November 2023; Accepted: 10 November 2023;
Published: 04 December 2023.
Edited and Reviewed by:
Claire Perks, University of Bristol, United KingdomCopyright © 2023 Recine, Bongiovanni, Mercatali, Fausti, Ferraresi and De Vita. 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) and the copyright owner(s) 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: Alessandro De Vita, YWxlc3NhbmRyby5kZXZpdGFAaXJzdC5lbXIuaXQ=