Recent advances in cancer immunology have led to a better understanding of the role of the tumor microenvironment (TME) in tumor initiation, progression, and metastasis. Tumors can occur at many locations within the body and coevolution between malignant tumor cells and non-malignant cells sculpts the TME at these sites. It has become increasingly clear that there are specific differences of the TMEs at different anatomical locations, and these tissue-specific TMEs regulate tumor growth, determine metastatic progression, and impact on the outcome of therapy responses. Herein, we review the scientific advances in understanding tissue-specific TMEs, discuss their impact on immunotherapeutic response, and assess the current clinical knowledge in this emerging field. A deeper understanding of the tissue-specific TME will help to develop effective immunotherapies against tumors and their metastases and assist in predicting clinical outcomes.
The microenvironment of a tumor has emerged recently as a critical contributor to the development of cancer. Within this environment, fibroblasts and immune cells are the cell lineages that seem to be active mediators of tumour development. The activated fibroblasts that are also present during wound healing and chronic inflammation have been studied extensively. Their activation leads to altered gene expression profiles that markedly increase growth factor and cytokine secretion, leading to major alterations in the immune cell microenvironment. To better understand normal tissue development, wound healing and the chronic inflammation that leads to cancer, we review here information available on the role of fibroblasts and immune cells in normal breast development and in cancer. We also discuss the immunogenicity of breast cancer compared to other cancers and the contribution of the immune microenvironment to the initiation, progression and metastasis of tumors. Also reviewed is the limited knowledge on the role of immune cells and fibroblasts in normal development and whether the risk of cancer increases when their control is not tightly regulated.
MCF-7 cells are a slow growing estrogen receptor (ER) positive human breast cancer cell line that is commonly used to model estrogen responsive breast cancer cell growth in-vitro and tumour growth in-vivo. These tumours require estrogen supplementation, and in-vivo doses of between 0.72mg and 2mg estradiol pellets are commonly implanted in the dorsal flank of ovariectomised, immunocompromised mice. We wanted to grow MCF-7 tumours in immunocompromised mice without the need to be ovariectomised. When we treated immunocompromised mice with 0.72mg pellets to induce MCF7 tumour growth, the mice developed urosepsis. We have now shown that lower doses of estradiol pellets, 0.3mg and 0.5mg, induce elevated serum estrogen levels and maintain tumour growth, without causing urosepsis. Supplementation for only one week did not support sustained MCF7 tumour growth. In conclusion, 0.3mg and 0.5mg silastic pellets can be used to stimulate ER+ breast cancer growth in ovary-intact, immune compromised mice.
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