(1) Background: The expression of programmed death-ligand 1 (PD-L1), which interacts with programmed cell death protein 1 (PD-1) on cytotoxic T lymphocytes (CTLs), enables tumors to escape immunosurveillance. The PD-1/PD-L1 interaction results in the inhibition of CTL proliferation, and effector function, thus promoting tumor cell evasion from immunosurveillance and cancer persistence. Despite 40% of gastric cancer patients exhibiting PD-L1 expression, only a small subset of patients responds to immunotherapy. Human epidermal growth factor receptor2 (HER2) is one of the critical regulators of several solid tumors, including metastatic gastric cancer. Although half of PD-L1-positive gastric tumors co-express HER2, crosstalk between HER2 and PD-1/PD-L1 in gastric cancer remains undetermined. (2) Methods: Human gastric cancer organoids (huTGOs) were generated from biopsied or resected tissues and co-cultured with CTLs and myeloid-derived suppressor cells (MDSCs). Digital Spatial Profiling (DSP) was performed on FFPE tissue microarrays of numerous gastric cancer patients to examine the protein expression of immune markers. (3) Results: Knockdown of HER2 in PD-L1/HER2-positive huTGOs led to a concomitant decrease in PD-L1 expression. Similarly, in huTGOs/immune cell co-cultures, PD-L1 expression decreased in huTGOs and was correlated with an increase in CTL proliferation which enhanced huTGO death. Treatment with Nivolumab exhibited similar effects. However, a combinatorial treatment with Mubritinib and Nivolumab was unable to inhibit HER2 expression in co-cultures containing MDSCs. (4) Conclusions: Our study suggested that co-expression of HER2 and PD-L1 may contribute to tumor cell immune evasion. In addition, autologous organoid/immune cell co-cultures can be exploited to effectively screen responses to a combination of anti-HER2 and immunotherapy to tailor treatment for gastric cancer patients.
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http://dx.doi.org/10.3390/cancers13246158 | DOI Listing |
Ther Adv Drug Saf
December 2024
Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
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World J Gastroenterol
December 2024
Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
Background: Advanced gastric tumors are extremely prone to metastasize the in 20%-30% of gastric cancer, and patients have a poor prognosis despite systemic chemotherapy. Peritoneal metastases from gastric cancer usually indicate the end stage of the disease without curative treatment.
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World J Gastroenterol
December 2024
Department of Gastroenterology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou 450000, Henan Province, China.
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World J Gastroenterol
December 2024
Faculty of Medicine, Duy Tan University, Da Nang 550000, Viet Nam.
Small cell lung cancer (SCLC) is a common type of primary lung cancer that contributes to approximately 15% of cases. It is closely associated with tobacco risk factors. It is also known as a type of lung cancer that has a high mortality rate within a short time due to its rapid growth rate (with tumor doubling time of 30 days) and its tendency to metastasize early in the disease process.
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