ABSTRACT
Purpose@#Appropriate preclinical mouse models are needed to evaluate the response to immunotherapeutic agents. Immunocompetent mouse models have rarely been reported for gastric cancer. Thus, we investigated immunophenotypes and responses to immune checkpoint inhibitor (ICI) in immunocompetent mouse models using various murine gastric cancer cell lines. @*Materials and Methods@#We constructed subcutaneous syngeneic tumors with murine gastric cancer cell lines, YTN3 and YTN16, in C57BL/6J mice. Mice were intraperitoneally treated with IgG isotype control or an anti–programmed death-ligand 1 (PD-L1) neutralizing antibody. We used immunohistochemistry to evaluate the tumor-infiltrating immune cells of formalin-fixed paraffin-embedded mouse tumor tissues. We compared the protein and RNA expression between YTN3 and YTN16 cell lines using a mouse cytokine array and RNA sequencing. @*Results@#The mouse tumors revealed distinct histological and molecular characteristics. YTN16 cells showed upregulation of genes and proteins related to immunosuppression, such as Ccl2 (CCL2) and Csf1 (M-CSF). Macrophages and exhausted T cells were more enriched in YTN16 tumors than in YTN3 tumors. Several YTN3 tumors were completely regressed by the PD-L1 inhibitor, whereas YTN16 tumors were unaffected. Although treatment with a PD-L1 inhibitor increased infiltration of T cells in both the tumors, the proportion of exhausted immune cells did not decrease in the non-responder group. @*Conclusion@#We confirmed the histological and molecular features of cancer cells with various responses to ICI. Our models can be used in preclinical research on ICI resistance mechanisms to enhance clinical efficacy.
ABSTRACT
Central sleep apnea (CSA) is attributed to medical or neurological conditions including stroke. The association of lesion location and CSA in patients with ischemic stroke has not been well elucidated. A 69-year-old man with a history of hypertension and diabetes mellitus was admitted due to stroke. The brain magnetic resonance imaging showed an acute ischemic stroke in the right ventral thalamus and adjacent hypothalamus. During hospitalization, polysomnography (PSG) was performed because repetitive cessation of respiration during sleep was observed by chance. PSG showed severe CSA; the apnea-hypopnea index (AHI) was 73.5 with a minimum oxygen saturation of 89% and central apnea index (CAI) was 63.0. Two years later, follow-up PSG showed that AHI was 7.2 with a minimum oxygen saturation of 91% and CAI was 1.0. We report the patient with CSA after ischemic stroke with right thalamus and adjacent hypothalamus, which resolved spontaneously with time.