Abstract
Immunotherapy is a highly promising approach for the treatment of gastric cancer, the third-leading cause of overall cancer death worldwide. In particular, tumor-infiltrating lymphocytes and peripheral blood mononuclear cells are believed to mediate host immune responses, although this activity may vary depending on the activation status and/ or their microenvironments. Here, we examined the expression of a specific zinc finger transcription factor, Helios (IKZF2), in gastric tumor-infiltrating lymphocytes by immunohistochemistry and the correlation with survival. Segregation of gastric cancer patients into high- vs. low-Helios-expressing tumor-infiltrating lymphocytes showed those with high expression to exhibit longer survival in gastric cancer patients, Helicobacter pylori-infected gastric cancer patients and advanced stage (III–IV) gastric cancer patients. In particular, Helios expression was an independent factor for survival in advanced gastric cancer patients. We performed immunofluorescence staining to detect Helios expression in tumor-infiltrating lymphocytes and peripheral blood mononuclear cells. We found that Helios is expressed more in CD4+ T cells and little in CD8+ T cells in infiltrated lymphocytes in gastric cancer. In summary, we believe that the study of specific characteristics of tumor-infiltrating lymphocytes can delineate the interactions of immune and tumor cells to improve upon immunotherapy strategies.
Highlights
While gastric cancer (GC) is the third-leading cause of global cancer-related deaths in 2018, it varies widely by geography, with the highest incidence rate in East Asia [1]
We found that Helios expressed both in Foxp3+ and Foxp3− lymphocytes infiltrated in gastric cancer [18]
To detect Helios expression in Tumor-infiltrating lymphocytes (TILs), we performed immunohistochemistry using an anti-Helios antibody in GC samples
Summary
While gastric cancer (GC) is the third-leading cause of global cancer-related deaths in 2018, it varies widely by geography, with the highest incidence rate in East Asia [1]. The GC tumor microenvironment is a predominant factor that impacts tumor development and therapeutic effects [2,3], and includes both cancerous and non-cancerous cells Life 2020, 10, 189 immune cells) [4] Both innate and adaptive immune cells normally present in the gastrointestinal tract have been reported to play important roles in the GC tumor microenvironment, either inhibiting or enhancing tumor development. Tumor-infiltrating lymphocytes (TILs) are crucial factors of the tumor microenvironment and reflect host antitumor immune responses. It has been reported that high levels of TILs reflected a protective role of host in antitumor immunity against GC and was associated with positive prognosis [6]
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