目的 总结女性生殖系统中恶性中胚叶混合瘤（MMMT）的临床病理特征及预后，分析P53及错配修复蛋白与MMMT发病之间的关系。方法 收集大理大学第一附属医院2015年9月—2022年9月15例经手术切除病理诊断为MMMT的病例，总结临床病理特点、免疫表型（P53、错配修复蛋白等）、治疗方案并随访。结果 15例MMMT原发于子宫10例，卵巢5例。发病年龄范围49~76岁，平均年龄60岁，中位年龄58岁。临床表现为阴道流血或流液，伴或不伴腹痛或盆腔包块。镜下肿瘤均由不同比例的恶性上皮和间叶源性肿瘤构成，P53野生型12例，突变型3例；错配修复蛋白（MSH6、MSH2、MLH1、PMS2）检测存在缺失的有4例。15例患者中均行手术治疗，12例行盆腔淋巴结清扫术，术后辅以放化疗。随访失访2例，死亡4例，复发6例，3例术后无复发和转移。结论 恶性中胚叶混合瘤临床少见，恶性程度高，病理诊断上存在困难，需要辅以免疫组织化学染色，P53及错配修复蛋白缺失与MMMT的发生存在一定关系。治疗上需要手术切除，辅以放化疗。
Objective To summarize the clinical and pathological characteristics and prognosis of malignant mesodermal mixed tumor（MMMT）in the female reproductive system，and analyze the relationship between P53 and mismatch repair proteins and the onset of MMMT．Methods A total of 15 cases diagnosed with MMMT after surgical resection at the First Affiliated Hospital of Dali University from September 2015 to September 2022 were collected．The clinical and pathological characteristics，immune phenotype（P53，mismatch repair protein，etc. ），treatment plan were summarized．And the patients were followed-up．Results Ten of 15 cases of MMMT were primary in the uterus and 5 of 10 in the ovaries．The age range of onset was 49 to 76 years old，with an average age of 60 and a median age of 58．Clinical manifestations included vaginal bleeding or fluid discharge，with or without abdominal pain or pelvic masses．Under the microscope，all tumors were composed of malignant epithelial and mesenchymal tumors in different proportions，with 12 cases of P53 wild-type and 3 cases of mutant type．There were 4 cases of missing mismatch repair proteins（MSH6，MSH2，MLH1，PMS2）detected．Among the 15 patients，all underwent surgical treatment，and 12 underwent pelvic lymph node dissection with postoperative adjuvant chemotherapy and radiotherapy．Two cases were lost to follow-up，four cases died，six cases recurred，and three cases had no recurrence or metastasis after surgery．Conclusions MMMT are rare in clinical practice，with high malignancy and poor prognosis．Pathological diagnosis is difficult，and immunohistochemical staining is needed．The absence of P53 and mismatch repair protein is related to the occurrence of MMMT. Surgical resection is required for treatment，supplemented by radiotherapy and chemotherapy．
实体瘤对免疫治疗应答非常有限，因此，如何有效提升肿瘤免疫治疗的疗效，已成为当前肿瘤免疫治疗领域亟待解决的关键难题与挑战。髓系来源抑制性细胞（MDSCs）的趋化募集及其所介导的肿瘤免疫逃逸机制，是制约实体瘤免疫治疗效果的核心因素之一。文章深入探讨了MDSCs的起源、表型特征、其介导肿瘤免疫逃逸的具体机制，以及当前针对MDSCs的靶向治疗策略与将MDSCs靶向疗法与肿瘤免疫治疗相结合的最新研究进展。此外，文章还系统性地分析了靶向MDSCs联合免疫治疗策略所面临的关键挑战，并据此提出了MDSCs的精准靶向策略。这一策略旨在精确激活抗肿瘤免疫反应，为癌症患者提供更为个性化、高效的治疗方案，从而开启肿瘤免疫治疗领域的新纪元，为癌症治疗策略的创新与发展贡献力量。
Solid tumors exhibit a very limited response to immunotherapy．Consequently，effectively enhancing the therapeutic efficacy of tumor immunotherapy has emerged as a critical challenge and problem that urgently needs to be addressed in tumor immunotherapy．The chemotaxis and recruitment of myeloid-derived suppressor cells（MDSCs）and the tumor immune evasionmechanisms mediated by them are one of the core factors that significantly restrict the efficacy of immunotherapy for solid tumors．In this review，we discuss the origins and phenotypic characteristics of MDSCs，the specific mechanisms by which they mediate tumor immune evasion，as well as current targeted therapeuticstrategies for MDSCs and the latest research progress in combining MDSC-targeted therapy with tumor immunotherapy．Furthermore，we have systematically analyzed the key challenges faced by the combination of MDSC-targeted and immunotherapy strategies，and accordingly proposed a precise targeting strategyfor MDSCs．This strategy aims to precisely activate anti-tumor immune responses，providing more personalized and efficienttreatment options for cancer patients，thereby opening a new era in tumor immunotherapy and contributing to the innovation anddevelopment of cancer treatment strategies．
乳酸以往被视为不具备生物学功能的代谢废物。随着人们对乳酸的深入研究,发现乳酸有多种作用。乳酸化修饰是近期发现一种与乳酸有关的蛋白质翻译后修饰过程。乳酸化修饰主要有两种,一种是与乳酸相关的直接修饰,另外一种是与丙酮酸相关的间接修饰。这两种乳酸化修饰均可能受到糖酵解、乳酸转运与堆积、蛋白质串扰以及神经系统等多方面的调控。乳酸化修饰可以通过直接或间接修饰组蛋白或非组蛋白,从而在肿瘤组织的代谢重编程、增殖、迁移及免疫逃逸中发挥着重要作用。乳酸化修饰的深入研究,有望为肿瘤的诊断和治疗开辟新的路径。因此,为了明确乳酸化修饰在肿瘤方面的研究进展,本文就蛋白乳酸化修饰的分子机制及其在肿瘤中作用的研究进展作一综述。
Lactic acid was previously regarded as a metabolic waste product with no biological function. As lactic acid has been intensively studied, it has been found to have multiple roles. Lactation modification is a recently discovered protein post-translational modification process related to lactic acid. There are two main types of lactation modification：one is direct modification related to lactic acid and the other is indirect modification related to pyruvate. Both types of lactation modification may be regulated by various aspects such as glycolysis, lactate transport and accumulation, protein crosstalk, and the nervous system. Lactation modification can play an important role in metabolic reprogramming, proliferation, migration, and immune escape of tumor tissues by directly or indirectly modifying histones or non-histone proteins. The in-depth study of lactation modification is expected to find new pathways for tumor diagnosis and treatment. Therefore, in order to clarify the research progress of lactation modification in tumors, this paper presents a review on the molecular mechanism of protein lactation modification and the research progress of its role in tumors.
