The introduction of immunotherapy in the treatment of solid and hematologic malignancies has unveiled the tremendous role played by the tumor microenvironment (TM) components in determining objective clinical responses, and drug resistance development. Recent progress in our understanding of cancer evolution on a genomic level has revealed that most genetic alterations of advanced disease are often present in premalignant lesions, suggesting again the pivotal role exerted by the TM in all these processes.

Interestingly, while some genomic alterations (such as KRAS and BRAF mutations) have been found to drive specific changes within the TM, a clear relationship between specific genomic lesions and the microenvironment composition is still not fully understood. It is therefore clear that a paradigm shift from targeting the tumor-cell to targeting the tumor-niche could represent a dramatic advancement in cancer therapy.

Many studies have already demonstrated the immune-modulatory properties of “old” tumor-targeting drugs such as cyclophosphamide, trabectedin or doxorubicin, as well as their potential to interfere with the tumor mutational burden. Additionally, the targeting of different immune components through immune-checkpoints inhibitors represents the standard of care in different cancers such as lung cancer, melanoma, or Hodgkin lymphoma.

Lastly, the combination of immune-activating drugs, such as lenalidomide with monoclonal antibodies, has shown unprecedented results in multiple myeloma, probably changing the evolution of the disease. However, many cancer patients still do not respond to TM oriented therapy and many other strategies, including vaccines, cytokines, and small molecules, are currently under intensive development.

In this Research Topic, we welcome Original Research, Reviews, Methods, Systematic Reviews, Clinical Trials, Case Reports and Opinion articles with a focus on (but not limited to) the following themes:

1) Preclinical and clinical effects of drugs targeting specific TM subpopulations
2) Tumor microenvironment composition and specific genetic lesions
3) Chemotherapy and TM targeting drugs combinations
4) Genomic alterations and response to checkpoint inhibitors
5) Differences in the microenvironment composition between tumors
6) Changes in the microenvironment composition during tumor evolution or progression
7) Role of the tumor microenvironment in drug resistance

This Research Topic is part two of a three-part series - please also see the collections:

"Targeting the Microenvironment Niche in Hematologic Malignancies"

"Targeting the Microenvironment Niche in Hematologic Malignancies"

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Frontiers in Oncology

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