Diffuse intrinsic pontine glioma(DIPG)is a pediatric brainstem tumor with a very poor prognosis,characterized by immunosuppressive tumor microenvironment(TME)that limits immune infiltration,including a significant red...Diffuse intrinsic pontine glioma(DIPG)is a pediatric brainstem tumor with a very poor prognosis,characterized by immunosuppressive tumor microenvironment(TME)that limits immune infiltration,including a significant reduction in circulating natural killer(NK)cells.This drop in NK cell levels and activity may promote tumor growth and immune evasion,making NK cells a promising target for immunotherapy.NK cells can attack and eliminate DIPG tumor cells,including glioma stem cells,while counteracting certain immune evasion strategies.Although theDIPGmicroenvironment and blood-brain barrier present challenges,NKcell-based therapies have shown encouraging tumor control and survival benefits in animal models with promising safety results.Current clinical trials for DIPG mostly focus on chimeric antigen receptor(CAR)-T cells targeting disialoganglioside(GD2)and cluster of differentiation 276(CD276 or B7-H3)antigens with early signs of success,while NK cell therapies,such as CAR-NK cells,are still in preclinical or early stages,requiring further development.The tumor’s immunosuppressive nature poses challenges that may need combination strategies or immune priming.Despite these obstacles,NK cell-based immunotherapy is an exciting and growing field.Upcoming clinical trials emphasize the potential for NK cell therapies to play a critical role in treating this aggressive pediatric brain cancer.展开更多
目的探讨胃肠道惰性NK细胞淋巴组织增殖性疾病(indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract,iNKLPD)的临床病理学特征。方法回顾性分析7例iNKLPD的临床病理学特征、内镜表现和免疫表型,进行原位杂交...目的探讨胃肠道惰性NK细胞淋巴组织增殖性疾病(indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract,iNKLPD)的临床病理学特征。方法回顾性分析7例iNKLPD的临床病理学特征、内镜表现和免疫表型,进行原位杂交检测,并复习相关文献。结果7例iNKLPD中男性2例,女性5例。年龄28~54岁,中位年龄40岁。临床表现:反酸2例,恶心3例,胃胀不适5例,腹痛1例。发病部位:单部位5例,多部位2例。发生于胃、小肠和结肠的病例显示小淋巴细胞在黏膜之间浸润。淋巴细胞胞质丰富、淡染,核染色质细腻,核仁不明显,核分裂罕见。背景中可见散在嗜酸性粒细胞。累及胆囊和膀胱的病例显示组织结构破坏。胆囊病例还可见具有淡染胞质、染色质较粗糙、有清晰核仁的细胞。免疫表型:CD3、CD56、CD7、TIA1和Granzyme B均阳性,CD20、CD8和CD5均阴性,4例CD4阴性,2例出现少数细胞胞质颗粒状阳性。Ki67增殖指数为10%~50%。7例EBER原位杂交均阴性。7例患者随访25~57个月,平均随访38个月,均存活,其中4例无临床症状,1例出现多部位累及,2例原部位复发。结论iNKLPD具有惰性临床进程,可累及胃肠道及以外的多个部位,需与胃肠道侵袭性淋巴瘤鉴别,避免误诊。展开更多
文摘Diffuse intrinsic pontine glioma(DIPG)is a pediatric brainstem tumor with a very poor prognosis,characterized by immunosuppressive tumor microenvironment(TME)that limits immune infiltration,including a significant reduction in circulating natural killer(NK)cells.This drop in NK cell levels and activity may promote tumor growth and immune evasion,making NK cells a promising target for immunotherapy.NK cells can attack and eliminate DIPG tumor cells,including glioma stem cells,while counteracting certain immune evasion strategies.Although theDIPGmicroenvironment and blood-brain barrier present challenges,NKcell-based therapies have shown encouraging tumor control and survival benefits in animal models with promising safety results.Current clinical trials for DIPG mostly focus on chimeric antigen receptor(CAR)-T cells targeting disialoganglioside(GD2)and cluster of differentiation 276(CD276 or B7-H3)antigens with early signs of success,while NK cell therapies,such as CAR-NK cells,are still in preclinical or early stages,requiring further development.The tumor’s immunosuppressive nature poses challenges that may need combination strategies or immune priming.Despite these obstacles,NK cell-based immunotherapy is an exciting and growing field.Upcoming clinical trials emphasize the potential for NK cell therapies to play a critical role in treating this aggressive pediatric brain cancer.
文摘目的探讨胃肠道惰性NK细胞淋巴组织增殖性疾病(indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract,iNKLPD)的临床病理学特征。方法回顾性分析7例iNKLPD的临床病理学特征、内镜表现和免疫表型,进行原位杂交检测,并复习相关文献。结果7例iNKLPD中男性2例,女性5例。年龄28~54岁,中位年龄40岁。临床表现:反酸2例,恶心3例,胃胀不适5例,腹痛1例。发病部位:单部位5例,多部位2例。发生于胃、小肠和结肠的病例显示小淋巴细胞在黏膜之间浸润。淋巴细胞胞质丰富、淡染,核染色质细腻,核仁不明显,核分裂罕见。背景中可见散在嗜酸性粒细胞。累及胆囊和膀胱的病例显示组织结构破坏。胆囊病例还可见具有淡染胞质、染色质较粗糙、有清晰核仁的细胞。免疫表型:CD3、CD56、CD7、TIA1和Granzyme B均阳性,CD20、CD8和CD5均阴性,4例CD4阴性,2例出现少数细胞胞质颗粒状阳性。Ki67增殖指数为10%~50%。7例EBER原位杂交均阴性。7例患者随访25~57个月,平均随访38个月,均存活,其中4例无临床症状,1例出现多部位累及,2例原部位复发。结论iNKLPD具有惰性临床进程,可累及胃肠道及以外的多个部位,需与胃肠道侵袭性淋巴瘤鉴别,避免误诊。