The Immune Infiltrate as a Paradigm Model to Study the Biology and Novel Therapeutic Approaches in Sarcomas, volume II

Tumor microenvironment (TME) plays a pivotal role in malignant progression and metastatization in several tumors, including Bone and Soft Tissue Sarcoma (STS). Understanding the complexity of sarcomas microenvironment is critical to improving the knowledge about the natural history and disease biology of this heterogeneous group of mesenchymal tumors. Moreover, the complex cross-talk between tumor and immune cells within the tumor microenvironment is crucial for the development of novel therapeutic approaches in the management of sarcomas.

The heterogeneity of sarcomas in terms of histotypes, clinical behavior, and responses to treatments can reflect also the high variability in the composition of TME and consequently in the potential response to immunotherapy.

Immunotherapy may have a role in the treatment of STS, which are often very challenging to manage, presenting frequent recurrences and limited treatment options. Therefore, in the landscape of STS treatment, Immunotherapy shows different scenarios of application, including strategies targeting TME.


While for a long time sarcomas have been considered "cold" from an immunological point of view, current novel discoveries contributed to better characterizing the immune complexity at the TME level, not only across the different histologies but also within single histology.

Tumor immune microenvironment (TiME) of sarcomas is characterized by different immune cell populations that can have prognostic relevance and may represent potential therapeutic targets, including macrophages, which represent the main immune infiltrate and a highly heterogeneous immune cells. Macrophage subtypes consist of immune-stimulatory M1 with pro-tumor activities and immune-suppressive M2 macrophages with anti-tumor properties. Their balance can be dysregulated in sarcomas and can be a source of innovative therapeutic approaches. On the other hand, a high expression level of genes related to antigen presentation and T‐cell infiltration seems to be present in specific STS histotypes, such as undifferentiated pleomorphic and leiomyosarcomas.

Moreover, increasing evidence are highlighting the involvement of the extracellular matrix (ECM) components in the sarcomas proliferation, invasion, and migration and they could represent promising predictive biomarkers of response to chemotherapy and/or innovative therapeutic targets.

These could represent promising predictive biomarkers of response to chemotherapy and innovative therapeutic targets.

This Research Topic will provide a comprehensive overview of the recent advances and future perspectives research in translational and clinical studies focusing on both TME and TiME in Sarcomas and their role in the landscape of biology and novel therapeutic approaches of these rare neoplasms.

We welcome Original Articles and Reviews.

Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.

Keywords: immune infiltrates, sarcoma, tumor microenvironment, TME, bone sarcoma, soft tissue sarcoma

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.