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.
Establishing predictive pre‐clinical models leads toward more accurate and practical immunotherapeutic development. Humanized mice (HM) provide a suitable platform to discern human‐specific disease pathogenesis and evaluate an array of novel therapeutics. This review discusses recent progresses in the production and deployment of HM in the study of cancer immunotherapy.
•Regulatory cells in breast cancer act more in favor of the tumor.•There is a complex network of cooperation between cells in the tumor microenvironment.•Regulatory cells can be high-potential ...targets for the treatment of breast cancer.
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.
Introduction
The timing of definitive aneurysm treatment (coiling or clipping) in poor-grade (Hunt-Hess IV or V) subarachnoid haemorrhage (SAH) patients has been a controversial topic. The purpose of ...this retrospective study was to analyse whether ultra-early coiling of ruptured intracranial aneurysms improves the clinical outcomes of poor-grade SAH patients.
Methods
The records of patients with aneurysmal SAH who were treated with endovascular coiling were retrieved. The patients were classified into two groups: group A (patients coiled within 24 h of SAH) and group B (patients coiled ≥ 24 h after SAH). For each group, the patient demographics, Fisher grade, aneurysm characteristics and clinical outcomes were recorded. Outcomes were measured at 6 months using the modified Rankin Scale (mRS).
Results
Thirty-one patients were coiled within 24 h of SAH (group A), and fourteen patients were coiled ≥24 h after SAH (group B). Groups A and B had similar clinical and angiographic characteristics. The clinical outcomes showed that a total of 58.1 % of the patients (18 of 31) in group A were independent (mRS 0–2) compared with 21.4 % of the patients (3 of 14) in group B (
P
= .028). Univariate analysis demonstrated that ultra-early coiling (
P
= .028) proved to be an independent predictor of better clinical outcomes (mRS 0–2).
Conclusions
Ultra-early (<24 h after SAH) coiling of ruptured aneurysms was associated with improved clinical outcomes compared to coiling at ≥24 h in poor-grade SAH patients. Larger, prospective studies are required to adequately assess the outcome differences between these two groups.
To investigate the serum granulocyte colony-stimulating factor (G-CSF) level in patients with chronic idiopathic neutropenia (CIN) and analyze its clinical significance. By the use of G-CSF-specific ...enzyme-linked immunosorbent assay (ELISA), the serum levels of G-CSF were determined in 40 cases with chronic CIN, 40 cases with systemic lupus erythematosus (SLE) complicated neutropenia and 40 healthy volunteer (normal control). Results showed that serum G-CSF was positive in 11 normal controls and in 10 cases with SLE, and the G-CSF levels were (27.34 +/- 8.00) ng/L and (26.76 +/- 7.26) ng/L, respectively. Serum G-CSF in 27 cases with CIN was positive, the level was (134.04 +/- 89.29) ng/L, which was higher than that in the normal controls and the cases with SLE (P < 0.01). It was concluded that an obstacle to utilization of G-CSF could be existed in the patients with CIN.
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