The effective cryopreservation of mesenchymal stem cells (MSCs) is indispensable to the operation of basic research and clinical transplantation. The prevalent protocols for MSC cryopreservation utilize dimethyl sulfoxide (DMSO), which is easily permeable and able to protect MSCs from cryo-injuries, as a primary cryoprotectant (CPA). However, its intrinsic toxicity and adverse effects on cell function remain the bottleneck of MSC cryopreservation. In this work, we cryopreserved human umbilical cord mesenchymal stem cells (UCMSCs) using zwitterionic betaine combined with electroporation without any addition of DMSO. Betaine was characterized by excellent compatibility and cryoprotective properties to depress the freezing point of pure water and balance the cellular osmotic stress. Electroporation was introduced to achieve intracellular delivery of betaine, intending to further provide comprehensive cryoprotection on UCMSCs. Compared with DMSO cryopreservation, UCMSCs recovered from the protocol we developed maintained the normal viability and functions and reduced the level of reactive oxygen species (ROS) that are harmful to cell metabolism. Moreover, the in vivo distribution of thawed UCMSCs was consistent with that of fresh cells monitored by a bioluminescence imaging (BLI) system. This work opens a new window of opportunity for DMSO-free MSC cryopreservation using zwitterionic compounds like betaine combined with electroporation.

Despite the tremendous amount of basic knowledge in cancer immunity gained and many transitional approaches attempted, current cancer immunotherapies are still far from reaching universal effectiveness. Therefore, next‐generation cancer immunotherapies would emerge from deepened mechanistic insights on the full spectrum of cellular and molecular interactions between cancer cells and their immune sentinels. This review embarks on an exhaustive exploration of the cardinal immunological principles that catalyze robust cancer surveillance and their potential escapes and recapitulate the state‐of‐art understanding of both receptors and corresponding immune cell types involved. Both tumor intrinsic and tumor microenvironmental mediators of immune escapes are outlined in the context of current clinic applications. Following emphasizing the exceptional requisites that effective cancer immunity cycle must meet, specific cellular subsets crucial for igniting tumor immunity, notably effector and helper T cells alongside antigen presentation cells are examined, focusing on their close interactions in both antigen‐dependent and ‐independent manners. Such intricate interactions form dynamic immune hubs at the tumor site, holding promising key functionality in rendering effective cancer retreat. Grounded on these recent insights, refined immunotherapeutic strategies, especially those bolstering priming based anticancer effector functions are advocated.

Immunotherapy using dendritic cell (DC)‐based vaccination is an established approach for treating cancer and infectious diseases; however, its efficacy is limited. Therefore, targeting the restricted migratory capacity of the DCs may enhance their therapeutic efficacy. In this study, the effect of laponite (Lap) on DCs, which can be internalized into lysosomes and induce cytoskeletal reorganization via the lysosomal reprogramming–calcium flicker axis, is evaluated, and it is found that Lap dramatically improves the in vivo homing ability of these DCs to lymphoid tissues. In addition, Lap improves antigen cross‐presentation by DCs and increases DC‐T‐cell synapse formation, resulting in enhanced antigen‐specific CD8⁺ T‐cell activation. Furthermore, a Lap‐modified cocktail (Lap@cytokine cocktail [C‐C]) is constructed based on the gold standard, C‐C, as an adjuvant for DC vaccines. Lap@C‐C‐adjuvanted DCs initiated a robust cytotoxic T‐cell immune response against hepatitis B infection, resulting in > 99.6% clearance of viral DNA and successful hepatitis B surface antigen seroconversion. These findings highlight the potential value of Lap as a DC vaccine adjuvant that can regulate DC homing, and provide a basis for the development of effective DC vaccines.