Over the past few decades, tumor immunotherapy has revolutionized the landscape of cancer clinical treatment. There is a flourishing development of combination strategies to improve the anti-tumor efficacy of mono-immunotherapy. However, instead of a straightforward combination of multiple therapeutics, it is more preferable to pursue a synergistic effect by designing rational combinations as well as administration strategies, which are based on a comprehensive understanding of the physiological and pathological features. In this case, the timing and spatial distribution of the combination drugs become essential factors in achieving improved therapeutic outcomes. Therefore, the concept of Sequential Drug Delivery System (SDDS) is proposed to define the spatiotemporally programmed drug delivery/release through triggers of internal conditions and/or external interventions, thus complying with the dynamic disease evolution and the human immunity. This review summarizes the recent advancements in biomaterial-based SDDSs used for spatiotemporally-tuned combination tumor immunotherapy. Furthermore, the rationales behind various engineering strategies are discussed. Finally, an overview of potential synergistic mechanisms as well as their prospects for combination immunotherapy is presented.

Platelets and neutrophils are now considered the key factor to thrombus initiation and progression .The present article describes the latest discovery of neutrophil extracellular trapping network (NETs) in thrombogenesis and unknown field to be explore ,including biological process of NET formation (NETosis) ,and how extracellular release of DNA and histone of NETs help coagulation and platelet aggregation .Cell biology of NETosis is still ac‐tively characterized ,which may provide new specific inhibition therapy insights .

Objective To study the characteristics of cell engraftment in mice at a lower dose under nonlethal radiated condition.Methods A syngeneic C57BL/6 mouse model,transplanted with 1 × 107 bone marrow cells and exposed to 2.5 Gy whole body irradiation (WBI),was selected to study the chimerism of cells from green fluorescent protein positive (GFP +) transgenic mice.The control group was injected with GFP + cells without receiving irradiation.In addition,an allogenic transplantation model of BALB/c mice was also investigated which was infused by GFP + cells from C57BL/6 mice.The engraftment of bone marrow-derived cells (BMDCs) was detected by immunohistochemistry in bone marrow,liver,lung,small intestine and spleen.Results The transplanted bone marrow cells successfully grafted in the haematopoietic tissues from syngeneic GFP transgenic mice.The transplanted GFP+ cells were also detected in the non-haematopoietic tissues,such as the small intestine,liver,spleen and lung,after irradiation.However,a lethal dose irradiation of 8 Gy was required to establish successful chimerism in allogeneic transplantation model by infusing the bone marrow cells from C57BL/6 mice to BALB/c mice.Conclusions Bone marrow-derived cells can be successfully grafted into various recipient tissues receiving a 2.5 Gy dose of radiation in syngeneic mice,but not in allogeneic mice.This nonlethal model may help to further study the plasticity and mechanism of bone marrow-derived cells in tissue repair and regeneration after radiation injury.