Discussion
tumor
TUMOR, INFILTRATION, METASTASIS
With the development of ICIs, a number of large phase III clinical studies have established the role of ICI combined with chemotherapy in the treatment of locally advanced or metastatic GC patients, but the population-wide data showed limited benefits. It has been hypothesized that one of the reasons for the poor efficacy of anti-PD-1/anti-PD-L1 therapy is the limited T lymphocyte infiltration in the tumor mcroenvironment (The present exploratory, random, open-label study investigated the use of autologous CIK cells combined with SOX versus SOX alone. Adding autologous CIK cells to SOX reduced the incidence of AEs. Previous studies have shown that activated CIK cells In previous studies, patients with a higher tumor load had a higher number of immunosuppressive cells, such as tumor-associated macrophages, regulatory T cells, or myeloid-derived suppressor cells, which promoted immune evasion while impeding immune monitoring (The present study results suggest that patients who received no fewer than three cycles of autologous CIK cells benefited the most from combination therapy. The timing of administration of the enhanced CIK cell preparation and favorable auto-lymphocyte characteristics may account for the improved OS and immune response. Treatment compliance in the study was satisfactory, which may be due to the low rate of serious AEs and well-tolerated characteristics, suggesting the feasibility of using autologous CIK cells in combination with chemotherapy. Subgroup analysis further suggested that the effect of autologous CIK cells may be more pronounced in patients with no fewer than two metastatic organs. This suggests that for patients with more extensive metastasis, improving the immune status of the body is more beneficial than chemotherapy alone, which needs to be confirmed by larger studies.The present study had several limitations. This was an exploratory study with a relatively small sample size and safety serving as the primary endpoint. Moreover, the single-center study lacked sufficient universality, making it difficult to generalize its findings. Due to the early start year of the study, biomarkers, such as TMB and PD-L1, have not been stratified, and partial immunohistochemical results, including those for HER2, are missing. Different marker states may affect the final results. In addition, the level of lymphocytes represents the state of immune function in the body, and further analysis of the number of lymphocyte subsets in patients was not available in the present investigation. Multicenter randomized controlled trials in larger cohorts are needed to further validate the efficacy and safety of the combination regimen and to further screen the population for benefit analysis.Future research should include determining the optimal number of cell therapy cycle and the interval between CIK cell treatments. In addition, population screening can be performed based on different markers, such as microsatellite status or PD-L1 expression, in order to explore the treatment efficacy in different types of patients receiving cell therapy.