Development of humanized mouse with patient-derived xenografts for cancer immunotherapy studies: A comprehensive review.

Immunotherapy has revolutionized cancer treatment, however, not all tumor types and patients are completely responsive to this approach. Establishing predictive pre-clinical models would allow for more accurate and practical immunotherapeutic drug development. Mouse models are extensively used as in vivo system for biomedical research. However, due to the significant differences between rodents and human, it is impossible to translate most of the findings from mouse models to human. Pharmacological development and advancing personalized medicine using patient-derived xenografts relies on producing mouse models in which murine cells and genes are substituted with their human equivalent. Humanized mice (HM) provide a suitable platform to evaluate xenograft growth in the context of a human immune system. In this review, we discussed recent advances in the generation and application of HM models. We also reviewed new insights into the basic mechanisms, pre-clinical evaluation of onco-immunotherapies, current limitations in the application of these models as well as available improvement strategies. Finally, we pointed out some issues for future studies.

Role of immune regulatory cells in breast cancer: Foe or friend?

Breast cancer (BC) is the most common cancer among women between the ages of 20 and 50, affecting more than 2.1 million people and causing the annual death of more than 627,000 women worldwide. Based on the available knowledge, the immune system and its components are involved in the pathogenesis of several malignancies, including BC. Cancer immunobiology suggests that immune cells can play a dual role and induce anti-tumor or immunosuppressive responses, depending on the tumor microenvironment (TME) signals. The most important effector immune cells with anti-tumor properties are natural killer (NK) cells, B, and T lymphocytes. On the other hand, immune and non-immune cells with regulatory/inhibitory phenotype, including regulatory T cells (Tregs), regulatory B cells (Bregs), tolerogenic dendritic cells (tDCs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), myeloid-derived suppressor cells (MDSCs), mesenchymal stem cells (MSCs), and regulatory natural killer cells (NKregs), can promote the growth and development of tumor cells by inhibiting anti-tumor responses, inducing angiogenesis and metastasis, as well as the expression of inhibitory molecules and suppressor mediators of the immune system. However, due to the complexity of the interaction and the modification in the immune cells' phenotype and the networking of the immune responses, the exact mechanism of action of the immunosuppressive and regulatory cells is not yet fully understood. This review article reviews the immune responses involved in BC as well as the role of regulatory and inhibitory cells in the pathogenesis of the disease. Finally, therapeutic approaches based on inhibition of immunosuppressive responses derived from regulatory cells are discussed.