The immune system in humans is a defense department against both exogenous and endogenous hazards, where CD8⁺ T cells play a crucial role in opposing pathological threats. Various immunotherapies based on CD8⁺ T cells have emerged in recent decades, showing their promising results in treating intractable diseases. However, in the fight against the constantly changing and evolving cancers, the formation and function of CD8⁺ T cells can be challenged by tumors that might train a group of accomplices to resist the T cell killing. As cancer therapy stepped into the era of immunotherapy, understanding the physiological role of CD8⁺ T cells, studying the machinery of tumor immune escape, and thereby formulating different therapeutic strategies become the imperative missions for clinical and translational researchers to fulfill. After brief basics of CD8⁺ T cell-based biology is covered, this review delineates the mechanisms of tumor immune escape and discusses different cancer immunotherapy regimens with their own advantages and setbacks, embracing challenges and perspectives in near future.

Extracellular vesicles (EVs), which are the main paracrine components of stem cells, mimic the regenerative capacity of these cells. Stem cell-derived EVs (SC-EVs) have been used for the treatment of various forms of tissue injury in preclinical trials through maintenance of their stemness, induction of regenerative phenotypes, apoptosis inhibition, and immune regulation. The efficiency of SC-EVs may be enhanced by selecting the appropriate EV-producing cells and cell phenotypes, optimizing cell culture conditions for the production of optimal EVs, and further engineering the EVs produced to transport therapeutic and targeting molecules.

In this study, we employed organic and inorganic dyes that have fluorescence under visible or near-infrared light region to stain human umbilical cord (Huc) mesenchymal stem cell (MSC)-, HEK293T cell- and HGC cell-derived small extracellular vesicles (sEVs), and then tracked their fluorescence signals in human gastric cancer xenografted murine models. Several biological characteristics were examined and compared when different dye-stained sEVs in the same tumor model or the same dye-stained sEVs between different tumor models were applied, including sEVs circulation in the blood, biodistribution of sEVs in major organs, and time-dependent tumor accumulation of sEVs. The results demonstrated that distinct tumor accumulation features were presented by sEVs if labeled by different fluorescent dyes, while sEVs derived from different cell lines showed homologous blood circulation and tumor accumulation. To conclude, although fluorescence imaging remains a reliable way to trace sEVs, single staining of sEVs membrane should be obviated in future work when examining the biological fate of sEVs.