The tumor tissue consists of cancer and host cells. They form an apparently poorly organized and dynamically evolving entity, the function of which is maintained in dynamic interplays among the components. Tumor-associated stroma is enriched with microvessels and infiltrating inflammatory cells. In addition to the cellular, also the extracellular matrix (ECM) components of the cancer microenvironment are important and decisive for the tumor tissue and for the outcome of the disease. The ECM constitutes a three-dimensional network; it might be a physical and chemical barrier against tumor cells infiltration, but also an adhesion point for migrating tumor cells. The interaction between host and tumor is contradictive, a mixture of supportive and abrogative effects.
Inflammation-related stimuli within the tumor microenvironment might support proliferation and survival of cancer cells, promote blood and lymphatic angiogenesis, and assist invasion and metastasis. These conditions contribute to upregulation of genes involved in tumor progression in carcinoma-associated fibroblasts (CAFs), to epithelial-to-mesenchymal transition of tumor cells and to functional impairment of dendritic cells, natural killer cells and lymphocytes. In contrast, inflammatory cells are originally recruited to the tumor tissue with the aim of organ and tissue repair. Although CAFs support tumor invasivity, a special group of fibroblasts, associated with tumor vessels, the pericytes, might serve as important gatekeepers against cancer progression and metastasis.
During carcinogenesis, genetic alterations produce high immunogenic clones, infiltration of the tumor with dendritic cells, macrophages, and lymphocytes should eliminate these immunogenic cells. Indeed, high immunogenic clones are eliminated in immunocompetent hosts leaving low immunogenic clones behind to grow. A dynamic several-year symbiosis of developing and progressing cancer with the immune system and with the local host environment leads to immunoresistant carcinoma, which is often the stage at clinical manifestation. This process can be recognized as the cancer evolution. Nevertheless, this is more complicated than just a pure selection of tumor cell clones. Understanding of the mechanisms taking place in the tumor microenvironment, elucidation of the dynamic interplays between tumor cells and stroma, identification of supportive and antitumor effects, and establishment of antitumor immune memory might end up in more effective therapeutic potential. This research topic will highlight the contradictions of the tumor microenvironment the responses of tumor cells to these inputs.
The tumor tissue consists of cancer and host cells. They form an apparently poorly organized and dynamically evolving entity, the function of which is maintained in dynamic interplays among the components. Tumor-associated stroma is enriched with microvessels and infiltrating inflammatory cells. In addition to the cellular, also the extracellular matrix (ECM) components of the cancer microenvironment are important and decisive for the tumor tissue and for the outcome of the disease. The ECM constitutes a three-dimensional network; it might be a physical and chemical barrier against tumor cells infiltration, but also an adhesion point for migrating tumor cells. The interaction between host and tumor is contradictive, a mixture of supportive and abrogative effects.
Inflammation-related stimuli within the tumor microenvironment might support proliferation and survival of cancer cells, promote blood and lymphatic angiogenesis, and assist invasion and metastasis. These conditions contribute to upregulation of genes involved in tumor progression in carcinoma-associated fibroblasts (CAFs), to epithelial-to-mesenchymal transition of tumor cells and to functional impairment of dendritic cells, natural killer cells and lymphocytes. In contrast, inflammatory cells are originally recruited to the tumor tissue with the aim of organ and tissue repair. Although CAFs support tumor invasivity, a special group of fibroblasts, associated with tumor vessels, the pericytes, might serve as important gatekeepers against cancer progression and metastasis.
During carcinogenesis, genetic alterations produce high immunogenic clones, infiltration of the tumor with dendritic cells, macrophages, and lymphocytes should eliminate these immunogenic cells. Indeed, high immunogenic clones are eliminated in immunocompetent hosts leaving low immunogenic clones behind to grow. A dynamic several-year symbiosis of developing and progressing cancer with the immune system and with the local host environment leads to immunoresistant carcinoma, which is often the stage at clinical manifestation. This process can be recognized as the cancer evolution. Nevertheless, this is more complicated than just a pure selection of tumor cell clones. Understanding of the mechanisms taking place in the tumor microenvironment, elucidation of the dynamic interplays between tumor cells and stroma, identification of supportive and antitumor effects, and establishment of antitumor immune memory might end up in more effective therapeutic potential. This research topic will highlight the contradictions of the tumor microenvironment the responses of tumor cells to these inputs.
