The International Agency for Research on Cancer(IARC)and World Health Organization(WHO)collaboratively produce the'WHO Blue Books'essential tools standardizing the diagnostic process for human cancers.Regular ...The International Agency for Research on Cancer(IARC)and World Health Organization(WHO)collaboratively produce the'WHO Blue Books'essential tools standardizing the diagnostic process for human cancers.Regular updates in this classification accommodate emerging molecular discoveries,advances in immunohistochemical techniques,and evolving clinical insights.The 5th edition of the WHO/IARC classification of head and neck tumors refines the'Oral Cavity and Mobile Tongue'chapter,including sections for non-neoplastic lesions,epithelial tumors,and tumors of uncertain histogenesis.Notably,the epithelial tumors section is rearranged by tumor behavior,starting with benign squamous papillomas and progressing through potentially malignant oral disorders to oral squamous cell carcinoma(OSCC).The section on OSCC reflects recent information on epidemiology,pathogenesis,and histological prognostic factors.Noteworthy is the specific categorization of verrucous carcinoma(VC)and carcinoma cuniculatum(CC),both associated with the oral cavity and distinct in clinical and histologic characteristics.This classification adjustment emphasizes the oral cavity as their predominant site in the head and neck.Designating specific sections for VC and CC aims to provide comprehensive insights into these unique subtypes,elucidating their clinical features,distinct histological characteristics,prevalence,significance,and clinical relevance.By categorizing these subtypes into specific sections,the 5th edition of the WHO classification aims to provide a more nuanced and detailed account,enhancing our understanding of these specific variants within the broader spectrum of head and neck tumors.展开更多
Head and neck squamous cell cancer(HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of ...Head and neck squamous cell cancer(HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of the disease. In most cases, treatment fails to obtain total cancer cure. In recent years, it appears that one of the key determinants of treatment failure may be the presence of cancer stem cells(CSCs) that escape currently available therapies. CSCs form a small portion of the total tumor burden but may play a disproportionately important role in determining outcomes. CSCs have stem features such as self-renewal, high migration capacity, drug resistance, high proliferation abilities. A large body of evidence points to the fact that CSCs are particularly resistant to radiotherapy and chemotherapy. In HNSCC, CSCs have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In the light of such observations, the present review summarizes biological characteristics of CSCs in HNSCC, outlines targeted strategies for the successful eradication of CSCs in HNSCC including targeting the self-renewal controlling pathways, blocking epithelial mesenchymal transition, niche targeting, immunotherapy approaches and highlights the need to better understand CSCs biology for new treatments modalities.展开更多
T-cell/histiocyte-rich large B-cell lymphoma is uncommon in children population. There were few cases reported in the literature with wide range clinical presentations including advanced stage, and more involvement of...T-cell/histiocyte-rich large B-cell lymphoma is uncommon in children population. There were few cases reported in the literature with wide range clinical presentations including advanced stage, and more involvement of liver, spleen and bone marrow. Head and neck lymphadenopathy tends to present in younger children. We report a case of 10-year-old boy who initially presented intermittent fever, headaches and neck lymphadenopathy. Subsequently, he developed diffuse lymphadenopathy and hepatosplenomegaly. T-cell/histiocyte-rich large B-cell lymphoma was diagnosed on a cervical lymph node biopsy. Cervical lymphadenopathy in this age group is most commonly reactive or nonmalignant processes. Lymphoma is much less frequent; mainly are non-Hodgkin lymphomas. However, a subset of large B-cell lymphoma called T-cell/histiocyte-rich B-cell lymphoma is rare in children.展开更多
Background:Metabolic reprograming and immune escape are two hallmarksof cancer.However,how metabolic disorders drive immune escape in head andneck squamous cell carcinoma(HNSCC)remains unclear.Therefore,the aim ofthe ...Background:Metabolic reprograming and immune escape are two hallmarksof cancer.However,how metabolic disorders drive immune escape in head andneck squamous cell carcinoma(HNSCC)remains unclear.Therefore,the aim ofthe present study was to investigate the metabolic landscape of HNSCC and itsmechanism of driving immune escape.Methods:Analysis of paired tumor tissues and adjacent normal tissues from69 HNSCC patients was performed using liquid/gas chromatography-mass spectrometry and RNA-sequencing.The tumor-promoting function of kynurenine(Kyn)was explored in vitro and in vivo.The downstream target of Kyn wasinvestigated in CD8^(+)T cells.The regulation of CD8+T cells was investigatedafter Siglec-15 overexpression in vivo.An engineering nanoparticle was establishedto deliver Siglec-15 small interfering RNA(siS15),and its association withimmunotherapy response were investigated.The association between Siglec-15and CD8^(+)programmed cell death 1(PD-1)^(+)T cells was analyzed in a HNSCCpatient cohort.Results:A total of 178 metabolites showed significant dysregulation in HNSCC,including carbohydrates,lipids and lipid-like molecules,and amino acids.Among these,amino acid metabolism was the most significantly altered,especiallyKyn,which promoted tumor proliferation and metastasis.In addition,most immune checkpoint molecules were upregulated in Kyn-high patientsbased on RNA-sequencing.Furthermore,tumor-derived Kyn was transferredinto CD8^(+)T cells and induced T cell functional exhaustion,and blockingKyn transporters restored its killing activity.Accroding to the results,mechanistically,Kyn transcriptionally regulated the expression of Siglec-15 via arylhydrocarbon receptor(AhR),and overexpression of Siglec-15 promoted immuneescape by suppressing T cell infiltration and activation.Targeting AhR in vivoreduced Kyn-mediated Siglec-15 expression and promoted intratumoral CD8^(+)Tcell infiltration and killing capacity.Finally,a NH_(2)-modified mesoporous silicananoparticle was designed to deliver siS15,which restored CD8^(+)T cell functionstatus and enhanced anti-PD-1 efficacy in tumor-bearing immunocompetentmice.Clinically,Siglec-15 was positively correlated with AhR expression andCD8+PD-1^(+)T cell infiltration in HNSCC tissues.Conclusions:The findings describe the metabolic landscape of HNSCC comprehensivelyand reveal that the Kyn/Siglec-15 axis may be a novel potentialimmunometabolism mechanism,providing a promising therapeutic strategy forcancers.展开更多
过继性T细胞疗法(adoptive T cell therapy,ACT)是一种高度个性化的抗肿瘤治疗方法,临床研究正在迅速发展。研究表明,ACT疗法可以通过增加T细胞数量,增强对肿瘤组织的特异性和反应性,从而克服肿瘤免疫缺陷抑制的产生。ACT疗法目前有3种...过继性T细胞疗法(adoptive T cell therapy,ACT)是一种高度个性化的抗肿瘤治疗方法,临床研究正在迅速发展。研究表明,ACT疗法可以通过增加T细胞数量,增强对肿瘤组织的特异性和反应性,从而克服肿瘤免疫缺陷抑制的产生。ACT疗法目前有3种主要模式:肿瘤浸润淋巴细胞(TILs)、嵌合抗原受体T细胞(CAR-T)和T细胞受体工程化T细胞(TCR-T)治疗。本文对ACT疗法的分类及研究进展进行综述,包括TILs、CAR-T、TCR-T以及基于类器官共培养的过继性T淋巴细胞免疫治疗,探讨ACT作为头颈部鳞癌治疗方式的应用前景。展开更多
Background: PD-1 and PD-L1 inhibitors have emerged as promising treatments for patients with head and neck squamous cell carcinoma (HNSCC).Methods: Systematic review and meta-analysis of PD-1 and PD-L1 inhibitors in H...Background: PD-1 and PD-L1 inhibitors have emerged as promising treatments for patients with head and neck squamous cell carcinoma (HNSCC).Methods: Systematic review and meta-analysis of PD-1 and PD-L1 inhibitors in HNSCC. Outcomes: median overall survival (mOS), median progression-free survival (mPFS), Response Evaluation Criteria in Solid Tumors (RECIST) and treatment-related adverse events (TRAEs).Results: Eleven trials reported data on 1088 patients (mean age: 59.9 years, range: 18-90). The total mOS was 7.97 months (range: 6.0-16.5). Mean mPFS for all studies was 2.84 months (range: 1.9-6.5). PD-1 inhibitors had a lower rate of RECIST Progressive Disease than PD-L1 inhibitors (42.61%, 95% confidence interval [CI]: 36.29-49.06 vs. 56.79%, 95% CI: 49.18-64.19,P < 0.001). The rate of TRAEs of any grade (62.7%, 95% CI: 59.8-65.6) did not differ.Conclusions: Meta-analysis shows the efficacy of PD-1 and PD-L1 inhibitors in HNSCC and suggests a possible difference in certain RECIST criterion between PD-1 and PD-L1 inhibitors. Future work to investigate the clinical significance of these findings is warranted.展开更多
文摘The International Agency for Research on Cancer(IARC)and World Health Organization(WHO)collaboratively produce the'WHO Blue Books'essential tools standardizing the diagnostic process for human cancers.Regular updates in this classification accommodate emerging molecular discoveries,advances in immunohistochemical techniques,and evolving clinical insights.The 5th edition of the WHO/IARC classification of head and neck tumors refines the'Oral Cavity and Mobile Tongue'chapter,including sections for non-neoplastic lesions,epithelial tumors,and tumors of uncertain histogenesis.Notably,the epithelial tumors section is rearranged by tumor behavior,starting with benign squamous papillomas and progressing through potentially malignant oral disorders to oral squamous cell carcinoma(OSCC).The section on OSCC reflects recent information on epidemiology,pathogenesis,and histological prognostic factors.Noteworthy is the specific categorization of verrucous carcinoma(VC)and carcinoma cuniculatum(CC),both associated with the oral cavity and distinct in clinical and histologic characteristics.This classification adjustment emphasizes the oral cavity as their predominant site in the head and neck.Designating specific sections for VC and CC aims to provide comprehensive insights into these unique subtypes,elucidating their clinical features,distinct histological characteristics,prevalence,significance,and clinical relevance.By categorizing these subtypes into specific sections,the 5th edition of the WHO classification aims to provide a more nuanced and detailed account,enhancing our understanding of these specific variants within the broader spectrum of head and neck tumors.
文摘Head and neck squamous cell cancer(HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of the disease. In most cases, treatment fails to obtain total cancer cure. In recent years, it appears that one of the key determinants of treatment failure may be the presence of cancer stem cells(CSCs) that escape currently available therapies. CSCs form a small portion of the total tumor burden but may play a disproportionately important role in determining outcomes. CSCs have stem features such as self-renewal, high migration capacity, drug resistance, high proliferation abilities. A large body of evidence points to the fact that CSCs are particularly resistant to radiotherapy and chemotherapy. In HNSCC, CSCs have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In the light of such observations, the present review summarizes biological characteristics of CSCs in HNSCC, outlines targeted strategies for the successful eradication of CSCs in HNSCC including targeting the self-renewal controlling pathways, blocking epithelial mesenchymal transition, niche targeting, immunotherapy approaches and highlights the need to better understand CSCs biology for new treatments modalities.
文摘T-cell/histiocyte-rich large B-cell lymphoma is uncommon in children population. There were few cases reported in the literature with wide range clinical presentations including advanced stage, and more involvement of liver, spleen and bone marrow. Head and neck lymphadenopathy tends to present in younger children. We report a case of 10-year-old boy who initially presented intermittent fever, headaches and neck lymphadenopathy. Subsequently, he developed diffuse lymphadenopathy and hepatosplenomegaly. T-cell/histiocyte-rich large B-cell lymphoma was diagnosed on a cervical lymph node biopsy. Cervical lymphadenopathy in this age group is most commonly reactive or nonmalignant processes. Lymphoma is much less frequent; mainly are non-Hodgkin lymphomas. However, a subset of large B-cell lymphoma called T-cell/histiocyte-rich B-cell lymphoma is rare in children.
基金National Natural Science Foundation of China,Grant/Award Numbers:82303280,82072980,82272831,82272983,82172897,82203614Science and Technology Daystar Program of Shanghai,Grant/Award Number:22QA1405300+4 种基金Natural Science Foundation of Shanghai,Grant/Award Numbers:22ZR1436800,20ZR1447300Young Talent Lift Project by the China Association for Science and Technology,Grant/Award Number:2020QNRC001Shanghai Sailing Program,Grant/Award Number:22YF1421600Young physicians collaborative innovation team of Shanghai Ninth People’s Hospital,Grant/Award Number:QC202004The Innovative Research Team of High-level Local Universities in Shanghai,Grant/Award Numbers:SHSMU-ZDCX20212500,SHSMU-ZLCX20212300。
文摘Background:Metabolic reprograming and immune escape are two hallmarksof cancer.However,how metabolic disorders drive immune escape in head andneck squamous cell carcinoma(HNSCC)remains unclear.Therefore,the aim ofthe present study was to investigate the metabolic landscape of HNSCC and itsmechanism of driving immune escape.Methods:Analysis of paired tumor tissues and adjacent normal tissues from69 HNSCC patients was performed using liquid/gas chromatography-mass spectrometry and RNA-sequencing.The tumor-promoting function of kynurenine(Kyn)was explored in vitro and in vivo.The downstream target of Kyn wasinvestigated in CD8^(+)T cells.The regulation of CD8+T cells was investigatedafter Siglec-15 overexpression in vivo.An engineering nanoparticle was establishedto deliver Siglec-15 small interfering RNA(siS15),and its association withimmunotherapy response were investigated.The association between Siglec-15and CD8^(+)programmed cell death 1(PD-1)^(+)T cells was analyzed in a HNSCCpatient cohort.Results:A total of 178 metabolites showed significant dysregulation in HNSCC,including carbohydrates,lipids and lipid-like molecules,and amino acids.Among these,amino acid metabolism was the most significantly altered,especiallyKyn,which promoted tumor proliferation and metastasis.In addition,most immune checkpoint molecules were upregulated in Kyn-high patientsbased on RNA-sequencing.Furthermore,tumor-derived Kyn was transferredinto CD8^(+)T cells and induced T cell functional exhaustion,and blockingKyn transporters restored its killing activity.Accroding to the results,mechanistically,Kyn transcriptionally regulated the expression of Siglec-15 via arylhydrocarbon receptor(AhR),and overexpression of Siglec-15 promoted immuneescape by suppressing T cell infiltration and activation.Targeting AhR in vivoreduced Kyn-mediated Siglec-15 expression and promoted intratumoral CD8^(+)Tcell infiltration and killing capacity.Finally,a NH_(2)-modified mesoporous silicananoparticle was designed to deliver siS15,which restored CD8^(+)T cell functionstatus and enhanced anti-PD-1 efficacy in tumor-bearing immunocompetentmice.Clinically,Siglec-15 was positively correlated with AhR expression andCD8+PD-1^(+)T cell infiltration in HNSCC tissues.Conclusions:The findings describe the metabolic landscape of HNSCC comprehensivelyand reveal that the Kyn/Siglec-15 axis may be a novel potentialimmunometabolism mechanism,providing a promising therapeutic strategy forcancers.
文摘过继性T细胞疗法(adoptive T cell therapy,ACT)是一种高度个性化的抗肿瘤治疗方法,临床研究正在迅速发展。研究表明,ACT疗法可以通过增加T细胞数量,增强对肿瘤组织的特异性和反应性,从而克服肿瘤免疫缺陷抑制的产生。ACT疗法目前有3种主要模式:肿瘤浸润淋巴细胞(TILs)、嵌合抗原受体T细胞(CAR-T)和T细胞受体工程化T细胞(TCR-T)治疗。本文对ACT疗法的分类及研究进展进行综述,包括TILs、CAR-T、TCR-T以及基于类器官共培养的过继性T淋巴细胞免疫治疗,探讨ACT作为头颈部鳞癌治疗方式的应用前景。
文摘Background: PD-1 and PD-L1 inhibitors have emerged as promising treatments for patients with head and neck squamous cell carcinoma (HNSCC).Methods: Systematic review and meta-analysis of PD-1 and PD-L1 inhibitors in HNSCC. Outcomes: median overall survival (mOS), median progression-free survival (mPFS), Response Evaluation Criteria in Solid Tumors (RECIST) and treatment-related adverse events (TRAEs).Results: Eleven trials reported data on 1088 patients (mean age: 59.9 years, range: 18-90). The total mOS was 7.97 months (range: 6.0-16.5). Mean mPFS for all studies was 2.84 months (range: 1.9-6.5). PD-1 inhibitors had a lower rate of RECIST Progressive Disease than PD-L1 inhibitors (42.61%, 95% confidence interval [CI]: 36.29-49.06 vs. 56.79%, 95% CI: 49.18-64.19,P < 0.001). The rate of TRAEs of any grade (62.7%, 95% CI: 59.8-65.6) did not differ.Conclusions: Meta-analysis shows the efficacy of PD-1 and PD-L1 inhibitors in HNSCC and suggests a possible difference in certain RECIST criterion between PD-1 and PD-L1 inhibitors. Future work to investigate the clinical significance of these findings is warranted.
