Emerging Roles and Mechanisms of Stromal Cells in Carcinomas at the Molecular Level

For an extended period, tumor microenvironment (TME) has not been focused on the field of cancer biology before Stephen Paget's "seed and soil" hypothesis. The representative characters of cells involved in TME are high plasticity and continuous phenotypic and functional change. For example, the desmoplastic reaction in pancreatic cancer is a critical histological observation, tightly associated with significantly increasing the interstitial fluid pressure within the tumor niche. Furthermore, the desmoplastic stroma and compressed vessel delay or block the circulating therapeutic agents' target location. Inflammation is well-known as a critical factor in developing TME enhancing tumorigenesis and cancer promotions in carcinomas. Stromal cells and immune cells usually surround and harmonize with cancer cells or mass, which form the inflammatory TME. Interactions between tumor cells and tumor-associated stromal cells (TASCs) have critical roles in tumor growth and progression. The complexity of stroma-tumor interaction shows remarkable heterogeneous tumor mass formation even though this process has high similarity with normal wound healing processes such as neoangiogenesis, fibroblast, and immune cell infiltration.

This Research Topic aims to enlighten the current and recent findings of the interplay between cancer inflammation and TME to understand the obstacles of cancer therapy of epithelial cancers. Cancer Immunology is one of the major strategies to cure cancer since engineered cell therapy has been popular recently, such as oncolytic viruses, antibody therapies, and CAR-T therapy. However, most current immunotherapies have limitations to target solid tumors like carcinomas. Tumor microenvironment-targeting therapy for carcinomas has the unmeasurable potential to synergize the current immunotherapy if we overcome the current hurdles. The etiologies of immunotherapy resistance are multi-layered, not only the issue of tumor cells but also the complexity of the interplay between carcinomas and their microenvironment in their solid mass. One reason to look at the stromal cells in carcinomas in the aspect of inflammation is that TASCs secrete many inflammation-related molecules, including IL-6, IL-8, stromal-derived factor-1 alpha VEGF, and else. These molecules lead carcinomas to recruit more tumor and pro-tumorigenic cells to develop TME. Solving the puzzles of tumor microenvironment and inflammation in carcinomas at the molecular levels will enable us to currently unsolved problems in understanding malignant carcinomas' mechanisms and therapeutic directions.

We welcome the submission of Original Research Articles, Reviews, Mini-Reviews, and Case Reports, but are not limited to. The scope of this special issue is studies of emerging roles of stromal cells in carcinomas, related, but not limited to, the following themes:

1. Understanding the role of stromal cells in modulating the interplay between the tumor microenvironment and cancer inflammation in carcinomas

2. Understanding the function and role of immune cells surrounding the solid tumor

3. Understanding the function and role of non-cellular molecules secreted by stromal cells in the tumor microenvironment of carcinomas

4. Understanding soluble molecules such as hormones and cytokines affecting stromal cells of the tumor microenvironment in carcinomas

5. Understanding stromal cell immunotherapies targeting the tumor microenvironment of carcinomas