The tumor microenvironment (TME) plays an essential role in the development of hemopoietic malignancies. Within the proliferation niches of lymph nodes, bone marrow, and secondary lymphoid organs, different cell types provide survival and growth factors to malignant cells. These subpopulations, including nonhematopoietic stromal cells, extra-cellular matrix, lymphocytes, and myeloid cells, present multiple phenotypic and functional alterations. Dynamic crosstalk between hematopoietic tumor cells and the TME actively shapes a tumor-supporting niche leading to immune escape mechanisms and drug resistance. Moreover, an altered availability of metabolites might contribute to a dysregulated immunological status and to detrimental functions of the microenvironment cells. The essential functions of the niche in supporting homeostasis in bone marrow and secondary lymphoid organs are thus turned in a detrimental support to cancer development.
Increasing evidence about the critical role of a deviant microenvironment in the initiation and maintenance of pathological conditions suggest to interfere with its deleterious protective functions. Therapeutic approaches to restore protective antitumor immunity through interference with the recruitment of myeloid cells, repolarization of immune cell subsets, and inhibition of tumor-promoting signals are promising strategies. This aim calls for a full characterization of the cellular composition of the permissive niches and an improved understanding of the mechanisms underlying their immunosuppressive and tumor-sustaining functions. An additional crucial point is to determine whether tolerogenic activity is dependent on their maturation and activation status.
The translational relevance of targeting TME is of high importance. However, the characterization of the cellular composition and the origin of the various cell types present in the microenvironment as well as the elucidation of the underlying molecular mechanisms leading to their detrimental functions needs additional understanding. The goal of this Research Topic is to provide a forum to advance research on these molecular mechanisms and their contribution to tumor microenvironment misinformation. We aim to explore innovative mechanism-based targeted interventions in therapeutic approaches.
In this Research Topic, subtopics could include but are not limited to the following:
- Identification of new phenotypes or subtypes of microenvironmental cells and their role in hematological malignancies.
- Mechanisms underlying the phenotypic transition or polarization and functions of microenvironmental cells, particularly involving epigenetic, metabolic, and transcriptional regulation.
- Mechanisms of cross-talk between tumoral and microenvironmental cells
- Development of new therapeutic strategies targeting the TME
This Research Topic accepts the following article types: original research, systematic review, and mini-review articles.
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 section and will not be accepted as part of this Research Topic.
Paolo Strati is a consultant for Roche-Genentech, Kite-Gilead, Hutchinson MediPharma, Astrazeneca-Acerta, ADC Therapeutics, Sobi, and TG Therapeutic. He has received financial support from Sobi, Astrazeneca-Acerta, ALX Oncology, and ADC Therapeutic.
The tumor microenvironment (TME) plays an essential role in the development of hemopoietic malignancies. Within the proliferation niches of lymph nodes, bone marrow, and secondary lymphoid organs, different cell types provide survival and growth factors to malignant cells. These subpopulations, including nonhematopoietic stromal cells, extra-cellular matrix, lymphocytes, and myeloid cells, present multiple phenotypic and functional alterations. Dynamic crosstalk between hematopoietic tumor cells and the TME actively shapes a tumor-supporting niche leading to immune escape mechanisms and drug resistance. Moreover, an altered availability of metabolites might contribute to a dysregulated immunological status and to detrimental functions of the microenvironment cells. The essential functions of the niche in supporting homeostasis in bone marrow and secondary lymphoid organs are thus turned in a detrimental support to cancer development.
Increasing evidence about the critical role of a deviant microenvironment in the initiation and maintenance of pathological conditions suggest to interfere with its deleterious protective functions. Therapeutic approaches to restore protective antitumor immunity through interference with the recruitment of myeloid cells, repolarization of immune cell subsets, and inhibition of tumor-promoting signals are promising strategies. This aim calls for a full characterization of the cellular composition of the permissive niches and an improved understanding of the mechanisms underlying their immunosuppressive and tumor-sustaining functions. An additional crucial point is to determine whether tolerogenic activity is dependent on their maturation and activation status.
The translational relevance of targeting TME is of high importance. However, the characterization of the cellular composition and the origin of the various cell types present in the microenvironment as well as the elucidation of the underlying molecular mechanisms leading to their detrimental functions needs additional understanding. The goal of this Research Topic is to provide a forum to advance research on these molecular mechanisms and their contribution to tumor microenvironment misinformation. We aim to explore innovative mechanism-based targeted interventions in therapeutic approaches.
In this Research Topic, subtopics could include but are not limited to the following:
- Identification of new phenotypes or subtypes of microenvironmental cells and their role in hematological malignancies.
- Mechanisms underlying the phenotypic transition or polarization and functions of microenvironmental cells, particularly involving epigenetic, metabolic, and transcriptional regulation.
- Mechanisms of cross-talk between tumoral and microenvironmental cells
- Development of new therapeutic strategies targeting the TME
This Research Topic accepts the following article types: original research, systematic review, and mini-review articles.
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 section and will not be accepted as part of this Research Topic.
Paolo Strati is a consultant for Roche-Genentech, Kite-Gilead, Hutchinson MediPharma, Astrazeneca-Acerta, ADC Therapeutics, Sobi, and TG Therapeutic. He has received financial support from Sobi, Astrazeneca-Acerta, ALX Oncology, and ADC Therapeutic.
