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iLIVER 2022年第4期1卷 225-234页

作者： Jingxin Yan Manjun Deng Shunyu Kong Ting Li Zhenwu Lei Lushun Zhang Yutong Zhuang Xin He Huanwei Wang Haining Fan Yingxing Guo Department of Interventional Therapies Affiliated Hospital of Qinghai UniversityXiningChina Department of Postgraduate Qinghai UniversityXiningChina Department of Hepatopancreatobiliary Surgery Affiliated Hospital of Qinghai UniversityXiningChina Qinghai Province Key Laboratory of Hydatid Disease Research XiningChina Department of Orthopedics Sichuan Provincial People's HospitalChengduChina Department of Postgraduate Chengdu Medical CollegeChengduChina Department of Pathology and Pathophysiology Chengdu Medical CollegeChengduChina Center of Sichuan for Elderly Care and Health Chengdu Medical CollegeChengduChina Department of Neurosurgery The Second School of Clinical MedicineSouthern Medical UniversityGuangzhou 510515GuangdongChina

Hepatocellular carcinoma(HCC)is one of the most common malignancies worldwide.With the development of systemic therapies,several studies are currently underway,especially those related to the use of programmed death-1/programmed cell death-ligand 1(PD-1/PD-L1)immunotherapy.Moreover,studies on transarterial che-moembolization(TACE)and PD-1/PD-L1 immunotherapy have demonstrated some interesting outcomes.This article reviewed the current clinical evidence on the combination of TACE and PD-1/PD-L1 immunotherapy.Overall,our review summarized that a favorable survival time could be achieved using this combination in most patients.However,complications such as hyperprogression should be taken seriously,and the underlying mechanisms need to be explored.

关键词： Hepatocellular carcinoma Transarterial chemoembolization programmed death 1 programmed cell death-ligand 1 Clinical evidence

Immune signature of small bowel adenocarcinoma and the role of tumor microenvironment

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World Journal of Gastroenterology 2024年第8期30卷 794-798页

作者： Grigorios Christodoulidis Marina Nektaria Kouliou Konstantinos Eleftherios Koumarelas Department of General Surgery University Hospital of LarissaLarissa 41110Greece

In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarcinoma(SBA)is a rare gastrointestinal neoplasm and despite the small intestine's significant surface area,SBA accounts for less than 3%of such tumors.Early detection is challenging and the reason arises from its asymptomatic nature,often leading to late-stage discovery and poor prognosis.Treatment involves platinum-based chemotherapy with a 5-fluorouracil combination,but the lack of effective chemotherapy contributes to a generally poor prognosis.SBAs are linked to genetic disorders and risk factors,including chronic inflammatory conditions.The unique characteristics of the small bowel,such as rapid cell renewal and an active immune system,contributes to the rarity of these tumors as well as the high intratumoral infiltration of immune cells is associated with a favorable prognosis.programmed cell death-ligand 1(PD-L1)expression varies across different cancers,with potential discrepancies in its prognostic value.Microsatellite instability(MSI)in SBA is associated with a high tumor mutational burden,affecting the prognosis and response to immunotherapy.The presence of PD-L1 and programmed cell death 1,along with tumor-infiltrating lymphocytes,plays a crucial role in the complex microenvironment of SBA and contributes to a more favorable prognosis,especially in the context of high MSI tumors.Stromal tumor-infiltrating lymphocytes are identified as independent prognostic indicators and the association between MSI status and a favorable prognosis,emphasizes the importance of evaluating the immune status of tumors for treatment decisions.

关键词： programmed cell death 1 programmed cell death-ligand 1 programmed death ligand Small bowel adenocarcinoma Tumor infiltrating lymphocytes Tumor microenvironment Microsatellite instability

Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment

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World Journal of Gastroenterology 2023年第40期29卷 5566-5581页

作者： Aitoshi Hoshimoto Atsushi Tatsuguchi Ryohei Hamakubo Takayoshi Nishimoto Jun Omori Naohiko Akimoto Shu Tanaka Shunji Fujimori Tsutomu Hatori Akira Shimizu Katsuhiko Iwakiri Department of Gastroenterology Nippon Medical SchoolTokyo 113-8603Japan Department of Analytic Human Pathology Nippon Medical SchoolTokyo 113-8603Japan Department of Pathology Nippon Medical SchoolChiba Hokusoh HospitalChiba 270-1694Japan

BACKGROUND Comprehensive genomic analysis has shown that small bowel adenocarcinoma(SBA)has different genomic profiles from gastric and colorectal cancers.Hence,it is essential to establish chemotherapeutic regimens based on SBA characteristics.The expression of programmed cell death-ligand 1(PD-L1)and programmed cell death-ligand 2(PD-L2)in SBA is not fully understood.Anti-PD-L1/PD-1 therapy uses tumor-infiltrating lymphocytes(TILs);therefore,the status of TILs in the tumor microenvironment(TME)may influence their efficacy.The ratio of FoxP3+to CD8+T cells has been reported to be useful in predicting the prognosis of digestive system cancers.AIM To investigate the clinicopathological significance of PD-L1/2 expression according to the status of TILs in SBA tissues.METHODS We performed immunohistochemical analysis for PD-L1,PD-L2,CD8,FoxP3,and DNA mismatch repair(MMR)proteins using formalin-fixed,paraffin-embedded tissues from 50 patients diagnosed with primary SBA.The immunoreactivities of PD-L1 and PD-L2 were determined separately in tumor cells and tumor-infiltrating immune cells throughout the tumor center and invasive margins,and finally evaluated using the combined positive score(CPS).We assessed CD8+and FoxP3+T cells in the intratumoral and tumor-surrounding stroma.Subsequently,we calculated and summed the ratio of FoxP3 to CD8+T cell counts.Immune-related cell densities were graded as low or high.Immunohistochemical results were compared with clinicopathological factors and patient prognosis.The distribution of cancer-specific survival(CSS)was estimated using the Kaplan–Meier method,and the log-rank test was used to test for significant differences in CSS.A Cox proportional hazard model was also used to assess the effect of tumor variables on CSS.RESULTS PD-L1 expression was positive in 34%in tumor cells(T-PD-L1)and 54%in tumor-infiltrating immune cells(I-PDL1)of the cases examined.T-PD-L2 was positive in 34%and I-PD-L2 was positive in 42%of the cases.PD-L1 CPS≥10 and PD-L2 CPS≥10 were observed in 50%and

关键词： Small bowel adenocarcinoma programmed cell death-ligand 1 programmed cell death-ligand 2 Tumor microenvironment Tumor-infiltrating lymphocytes Regulatory T-cells

Treatment of gastric carcinoma with lymphoid stroma by immunotherapy:A case report

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World Journal of Clinical Cases 2022年第25期10卷 8962-8967页

作者： Yu-Jie Cui Yan-Yan Ren Hong-Zhen Zhang Department of Oncology Hebei General HospitalShijiazhuang 050051Hebei ProvinceChina Department of Medicine Hebei North UniversityZhangjiakou 075000Hebei ProvinceChina

BACKGROUND Gastric cancer with lymphoid stroma(GCLS)is a rare type of gastric cancer characterized by abundant lymphocytic infiltration of the stroma.It is an EpsteinBarr virus-associated gastric cancer with a better prognosis than typical gastric cancer but with similar symptoms.GCLS diagnosis is based on pathological,histological and immunohistochemical examination and there are no standardized guidelines for treatment.CASE SUMMARY This case report describes a 72-year-old man with a 6-mo history of abdominal pain.Endoscopy revealed ulcerative lesions in the stomach and gastric cancer was suspected.A preoperative endoscopic biopsy indicated undifferentiated carcinoma and postoperative pathological,histological and immunohistochemical analyses of the resected specimen confirmed a final diagnosis of GCLS.CONCLUSION The patient showed high programmed cell death-ligand 1 expression and recovered well after immunotherapy.

关键词： Lymphoid stroma Gastric cancer Epstein-Barr virus programmed cell death-ligand 1 Immunotherapy Prognosis Case report