Lung cancer is the malignant tumor with the highest mortality rate worldwide. The tumor microenvironment (TME) is a key factor in the progression of lung cancer, composed of tumor cells, signaling molecules, fibroblasts, immune cells, etc. Among them, tumor associated neutrophil (TAN), as an important component of immune cells in the TME, plays multiple roles in tumor cell proliferation, invasion, angiogenesis, and metastasis due to its aberrant function, and is closely associated with poor prognosis. However, there are limited researches on the mechanism of TAN in lung cancer. This review aims to provide more scientific basis for studying the therapeutic targets of lung cancer and developing new drugs by elucidating the different subtypes of TAN and their mechanisms of action in the occurrence and development of lung cancer.
.
Humans ; Neutrophils/pathology* ; Lung Neoplasms/pathology* ; Tumor Microenvironment ; Animals

[摘 要] 基因修饰T细胞疗法在肿瘤治疗领域取得突破性进展，主要包括嵌合抗原受体基因修饰T（chimeric antigen receptor engineered T，CAR-T）细胞和T细胞受体基因修饰T（T-cell receptor modified T，TCR-T）细胞。虽然CAR-T细胞疗法在血液系统肿瘤治疗领域呈现良好的临床治疗效果，但CAR-T细胞仅能识别肿瘤细胞膜抗原（占细胞全部抗原的比例约10%），而TCR-T细胞可以识别人白细胞抗原（human leukocyte antigen，HLA）提呈的细胞内抗原，因此TCR-T细胞可以识别更多种类的肿瘤抗原，进而实现对CAR-T细胞的合理补充。由于TCR-T细胞需要同时识别细胞内抗原和对应的HLA，而不同患者的HLA分型和表达的肿瘤抗原都可能存在巨大差异，因此有必要为每个/每类肿瘤患者定制个体化的TCR-T细胞，其中的关键为筛选特异识别肿瘤抗原的TCR。当前主要有筛选靶向“已知”肿瘤抗原TCR和筛选靶向“未知”肿瘤抗原TCR的两种策略，但其各有适用性，应针对每个患者制定适合的筛选方法，以制备多种肿瘤特异性TCR-T细胞，从而实现个体化TCR-T细胞的肿瘤治疗。

Objective To investigate the clinical characteristics,diagnosis and treatment strategies of breast neuroendocrine carcinoma.Methods 20 cases with breast neuroendocrine carcinoma,who were admitted in Department of Breast Surgery,the Second Affiliated Hospital of Dalian Medical University from Mar.2005 to Dec.2017,were analyzed retrospectively.Results The average age of the 20 patients was(54.35±13.35) years.In aspect of surgery,18 patients received modified radical mastectomy,1 patient received total glandectomy and sentinel lymph node biopsy and stage I silicone implant breast reconstruction,and 1 patient received radical mastec tomy.In terms of pathological types,there were 5 cases (25.0％) of highly differentiated neuroendocrine carcinoma,4 cases (20.0％) of poorly differentiated neuroendocrine carcinoma (small cell carcinoma),and 11 cases (55.0％)of invasive breast cancer with neuroendocrine differentiation.In molecular typing,there were 7 cases (35.0％) of Luminal A,7 cases (35.0％) of Luminal B (HER2 negative),4 cases (20.0％) of Luminal B (HER2 positive),and one case(5.0％) of HER2 type and one case(5.0％) of Basal-like type.The positive rates of ER,PR and HER2 in this group were 90.0％,60.0％ and 25.0％ respectively.20 patients were followed up for 5 to 119 months,with an average follow-up of (59.85±24.51) months.One patient developed bone metastases in the 6th year after surgery and survived for 119 months.One patient developed pulmonary metastasis at the 20th month after surgery and died at the 28th month after surgery.So far,the remaining postoperative patients still survived and no sign of recurrence or metastasis was found.Conclusion The diagnosis of breast neuroendocrine carcinoma relies on histopathological and immunohistochemical detection.Its ER/PR positive rate is high,its molecular typing is mostly Luminal type,and neoadjuvant treatment can be performed when necessary.For specific patients whose ER or PR are positive,neoadjuvant endocrine therapy is also a well-established therapy,even the optimal results can be achieved.However,more cases are still needed for research.