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Deconstructing tumor heterogeneity: the stromal perspective
Renee E Vickman1,2, Douglas V Faget3,2, Philip Beachy4
1Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA.
Abstract:
Significant advances have been made towards understanding the role of immune cell-tumor interplay in either suppressing or promoting tumor growth, progression, and recurrence, however, the roles of additional stromal elements, cell types and/or cell states remain ill-defined. The overarching goal of this NCI-sponsored workshop was to highlight and integrate the critical functions of non-immune stromal components in regulating tumor heterogeneity and its impact on tumor initiation, progression, and resistance to therapy. The workshop explored the opposing roles of tumor supportive versus suppressive stroma and how cellular composition and function may be altered during disease progression. It also highlighted microenvironment-centered mechanisms dictating indolence or aggressiveness of early lesions and how spatial geography impacts stromal attributes and function. The prognostic and therapeutic implications as well as potential vulnerabilities within the heterogeneous tumor microenvironment were also discussed. These broad topics were included in this workshop as an effort to identify current challenges and knowledge gaps in the field.
Insights
Non-immune stromal cells critically regulate tumor heterogeneity, impacting growth and therapy resistance. Understanding these stromal elements is key to identifying new cancer treatment strategies.
Area of Science:
- Oncology
- Cancer Biology
- Tumor Microenvironment
Background:
- Immune cells' role in tumor progression is known, but non-immune stromal components remain poorly understood.
- Stromal elements significantly influence tumor heterogeneity, initiation, progression, and therapeutic resistance.
Purpose of the Study:
- To highlight and integrate the functions of non-immune stromal components in regulating tumor heterogeneity.
- To explore the dual roles of tumor-supportive versus tumor-suppressive stroma.
- To identify challenges and knowledge gaps regarding the tumor microenvironment.
Main Methods:
- NCI-sponsored workshop integrating diverse research perspectives.
- Discussions on cellular composition, function, and spatial geography of the tumor microenvironment.
- Exploration of prognostic and therapeutic implications of stromal elements.
Main Results:
- Non-immune stromal components critically regulate tumor heterogeneity.
- Stromal composition and function can change during disease progression, influencing tumor behavior.
- Microenvironment and spatial factors dictate lesion aggressiveness and therapeutic response.
Conclusions:
- Further research is needed to define the roles of non-immune stromal cells in cancer.
- Understanding the tumor microenvironment is crucial for developing effective cancer therapies.
- Identifying vulnerabilities within the heterogeneous tumor microenvironment presents therapeutic opportunities.
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