ABSTRACT
The impact of the immune response on the therapeutical efficacy of neoadjuvant chemotherapy for breast cancer remains largely unknown. To characterize the role of regulatory T cells (CD4+CD25+CD127lowTreg), T lymphocyte subsets (CD3+, CD4+, CD4+/CD8+) and NK cells in neoadjuvant chemotherapy, we investigated the correlation patterns of these immune cell subsets with the progression of breast cancer. A total of 120 breast cancer patients receiving neoadjuvant chemotherapy in Nanjing Maternal and Child Health Hospital from May 2019 to November 2021 were retrospectively collected as the breast cancer group, and 46 healthy women were selected as the control group. The number of regulatory T cells, T lymphocyte subsets and NK cells in the peripheral blood were analyzed by flow cytometry. Compared with the control group, CD3+, CD4+, CD4+/CD8+ ratio and NK cells were significantly decreased in patients with breast cancer (P < 0.05), while the levels of Treg and CD8+ cells were significantly increased (P < 0.05). In addition, the status of the immune response among breast cancer patients at different clinical stages was obviously different. In higher tumor stages, the level of CD3+, CD4+, CD4+/CD8+ ratio and NK cell were reduced, while the level of Treg and CD8+ T cells gradually increased. Furthermore, we found a lower percentage of CD3+, CD4+, CD4+/CD8+ and NK cells in association with lymph node metastasis, accompanied by a higher number of CD8+ T cells. Interestingly, after treatment with neoadjuvant chemotherapy, the levels of Tregs, CD3+, CD4+ and CD4+/CD8+ ratio of patients were all upregulated compared with the levels before treatment, indicating the recovery of cytotoxic lymphocytes and a consolidation of the immunosuppressive microenvironment at the same time (P < 0.05). Immune dysfunction is commonly observed in breast cancer patients, which is closely associated with tumor progression and lymph node metastasis. Neoadjuvant chemotherapy was found to highly influence the number of T lymphocytes and improve the immune function of T lymphocyte subsets in breast cancer patients. At the same time, as immunosuppressive cells, the proportion of Tregs (CD4+CD25+CD127lowTreg) also increased after treatment with neoadjuvant chemotherapy. Our results provide guidance for the development of new combination strategies during neoadjuvant chemotherapy to reverse the immunosuppressive microenvironment and achieve better clinical outcomes.
ABSTRACT
Injury to lower genitourinary (GU) tissues, which may result in either infertility and/or organ dysfunctions, threatens the overall health of humans. Bioactive agent-based regenerative therapy is a promising therapeutic method. However, strategies for spatiotemporal delivery of bioactive agents with optimal stability, activity, and tunable delivery for effective sustained disease management are still in need and present challenges. In this review, we present the advancements of the pivotal components in delivery systems, including biomedical innovations, system fabrication methods, and loading strategies, which may improve the performance of delivery systems for better regenerative effects. We also review the most recent developments in the application of these technologies, and the potential for delivery-based regenerative therapies to treat lower GU injuries. Recent progress suggests that the use of advanced strategies have not only made it possible to develop better and more diverse functionalities, but also more precise, and smarter bioactive agent delivery systems for regenerative therapy. Their application in lower GU injury treatment has achieved certain effects in both patients with lower genitourinary injuries and/or in model animals. The continuous evolution of biomaterials and therapeutic agents, advances in three-dimensional printing, as well as emerging techniques all show a promising future for the treatment of lower GU-related disorders and dysfunctions.
