Trends in Cancer
ReviewTurning Cold into Hot: Firing up the Tumor Microenvironment
Section snippets
Exploring the TME
For many decades, efforts have been made to identify the genetic driver mutations of cancer initiation and progression. However, cancer progression is not solely determined by genetic alterations within tumor cells but is also critically regulated by the surrounding niche, which may provide important factors promoting cancer development or escape from the surveillance of the host immune system [1]. Since Rudolf Virchow observed leukocytes in neoplastic tissues and first proposed the link
Understanding the Complexity and Heterogeneity of the TME: ‘Cold’ versus ‘Hot’
The density and diversity of tumor-infiltrating immune cells are closely related to prognosis and prediction of treatment efficacy. Thus, understanding the differential composition of immune cells between the primary and metastatic TME may represent an important factor that greatly affects the response to distinct immunotherapy strategies [8,9]. Moreover, different patients with the same cancer type may differ greatly in immune cell composition within the TME, indicating that mapping the
Therapeutically Exploiting the TME to Boost Antitumor Immunity
Tumor cells develop various strategies to evade immune surveillance and the aforementioned highly immunosuppressive/metabolically stressed TME remain major barriers hindering effective antitumor immunity. In this section, we discuss several key steps of TME modulation with a particular focus on innate immune-sensing machinery, genetic alterations of oncogenic signaling, cellular metabolism, and epigenetic regulators. In addition, we present potential strategies to target those regulators within
Concluding Remarks
We now recognize that the TME is a highly dynamic network during tumor progression or upon therapeutic interventions. Thus, developing novel high throughput single-cell approaches, which could combine multiomics profiling in a spatial context within the TME, will enable in depth characterization of phenotypic, functional features of diverse cell types and better reveal their crosstalk at various stages of cancer development and metastasis (see Outstanding Questions). Nevertheless, it remains
Acknowledgments
The authors would like to thank Dr Isabel C. Lopez-Mejia for critical reading of the manuscript. L.Z. is supported by Natural Science Foundation of China (NSFC 81971466) and Innovation Fund from the Chinese Academy of Medical Sciences (2016-I2M-1-005). J. Zheng. is supported by National Key R&D Program of China (2018YFA0900900) and Jiangsu Provincial Key Medical Discipline, the Project of Invigorating Health Care through Science, Technology and Education (No. ZDXKA2016014).
Glossary
- Epigenetics
- certain chromatin modifications that can modulate gene expression without altering DNA coding sequence.
- Immune surveillance
- surveillance from both innate and adaptive immunity to recognize and monitor tumor growth.
- Immunogenicity
- the ability of a foreign substance to confer a certain level of immunity to the host.
- Metastasis
- spreading of primary tumor in adjacent or distant organ/tissue.
- Tumor microenvironment
- an intricate ecosystem that is highly heterogenous and dynamic, which consists of
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These authors contributed equally to this manuscript