This study analyzed the relationship between TDs and clinicopathologic characteristics and prognosis of gastric cancer. The results found that 22.0% of the 369 gastric cancer samples was 22.0%, TDs was significantly associated with gender, Lymphovascular invasion, Perineural invasion, pathological TNM and clinical stages, and significant survival differences between TDs + and TDs-. TDs was an independent prognostic factor of DFS, CSS, OS of gastric cancer.Based on this basis, this topic further studies the relationship between TDs and TILs in the tumor microenvironment, and the results found that the TDs is negatively related to the TILs, suggesting that there may be a complex relationship between TDs and tumor microenvironment, TDs and TILs may interact and affect the prognosis of patients with gastric cancer.
In 1935, Gabriel et al. first identified and reported TDs in colorectal cancer specimens, which they thought were the results of cancer cell dissemination along blood vessels . The 8th edition of the AJCC/Union for International Cancer Control defines TDs as discrete tumor nodules within the lymph drainage area of the primary carcinoma without identifiable lymph node tissue or identifiable vascular or neural structure . In the pN staging of colorectal cancer, the absence of regional lymph node metastasis along with the presence of TDs within the subplasma and mesenteric tissues is classified as N1c. If both regional lymph node metastasis and TDs are present, the presence of TDs has no effect on staging, and the incidence of TDs in colorectal cancer ranges from 5–45% and is associated with a poor prognosis in colorectal cancer [13–15]. Previous studies have found that TDs are present not only in colorectal cancer but also in other solid malignancies, such as gastric, bile duct, and pancreatic cancers [2, 16]. Currently, although a few studies have shown that the presence of TDs is an independent prognostic factor for a poor prognosis in gastric cancer [9, 10], the mechanism of TDs formation is unclear.For colorectal cancer, the importance of TDs has been recognized and has been included in category N in the 7th edition of the TNM staging system for colorectal cancer. However, in the 8th edition of the TNM staging system, TDs are considered as a metastatic lymph node in gastric cancer, which is contrary to the findings of the current study. A recent retrospective study that included 7,445 gastric cancer cases showed that the incidence of TDs ranging from 10.6–36.7% (mean: 20.9%) . Liang studied 1,034 gastric cancer patients, of whom 240 (23.21%) had TDs + and found that TDs were an independent prognostic factor for gastric cancer patients , which is similar to our findings. Therefore, the present study demonstrates that TDs is frequently observed and is an indicator of the aggressive characteristics of GC. The presence of TD is a strong and independent prognostic factor and should be incorporated into staging strategies in GC.
Regarding the study on the number, size, and prognosis of TDs.Benoit et al. found that the number of TDs ≥ 4 had a lower DFS in rectal cancer . In the present study, we investigated the relationships among the number of TDs, maximum diameter of TDs, and prognosis of gastric cancer. The results showed that the number of TDs was closely related to DFS, CSS, and OS of gastric cancer, and there was a significant difference in survival between the two groups. But in our study ,the maximum diameter of TDs was not related to prognosis,this is similar to Raul’s study,suggesting that pathologists need to pay more attention to the number of TDs when observing the sections. The critical value of TDs should be verified by larger sample studies.
TILs are T lymphocytes, B lymphocytes, and NK cells that accumulate in the area of the tumour lesion and are at the forefront of the immune response and regulatory role in the tumour immune mechanism .Studies have shown that the antitumor immune effect of TILs is mainly cellular, on the one hand, dendritic cells present the major histocompatibility complex molecules of captured tumor neoantigens to T cells, leading to the activation of effector T cells and killing of tumor cells, which in turn secrete suppressive cytokines and have antitumor effects; however, in the majority of cancer patients, the immune system cannot However, in the majority of cancer patients, the immune system fails to function effectively: it may be due to the failure of the immune system to recognize the tumor antigen and treat the tumor antigen as its own, i.e., immune tolerance; the inability of the effector T cells to infiltrate into the tumor lesion, or the suppressor (or immunosuppressive cells) in the tumor microenvironment inhibiting the function of effector cells . In addition, the immune system, while removing tumor cells, also "reshapes" the characteristics of tumor cells to make them more malignant and more resistant to immune attack, i.e., "immune editing" . Therefore, the immune system has a "double-edged sword" role in the process of tumor cell development, because TIL is a major player in tumor immunity, and there are many different subgroups of TILs, and the role of different subgroups in tumor development varies greatly, so the impact on tumor is also different.In the present study, TDs have been shown to be an independent prognostic factor for gastric cancer patients, and TDs + was associated with poor prognosis in gastric cancer, which is consistent with previous studies [9, 10]. And the present study also found that TDs were negatively correlated with TILs, and TILs levels were lower in TDs(+) group and higher in TDs(-) group.From which we can conclude that in the tumor microenvironment of gastric cancer, TDs and TILs interact with each other to regulate the development of gastric cancer, thus affecting gastric cancer prognosis of patients. However, the mechanism of the interaction between TDs and TILs has not yet been elucidated, and more studies are needed to explore it in the future.
However,there is one limitation that require further discussion. the findings of this retrospective study from a single Chinese institution may not be generalizable to other settings.Therefore, these findings should be considered only for hypothesis generation and require additional validation with more extensive studies.