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High-grade serous tubo-ovarian cancer (HGSTOC) is an aggressive gynecological malignancy including homologous recombination deficient (HRD) and homologous recombination proficient (HRP) groups. Despite the therapeutic potential of poly (ADP-ribose) polymerase inhibitors (PARPis) and anti-PDCD1 antibodies, acquired resistance in HRD and suboptimal response in HRP patients necessitate more precise treatment. Herein, single-cell RNA and single-cell T-cell receptor sequencing on 5 HRD and 3 HRP tumors are performed to decipher the heterogeneous tumor immune microenvironment (TIME), along with multiplex immunohistochemistry staining and animal experiments for validation. HRD tumors are enriched with immunogenic epithelial cells, FGFR1+PDGFRß+ myCAFs, M1 macrophages, tumor reactive CD8+/CD4+ Tregs, whereas HRP tumors are enriched with HDAC1-expressing epithelial cells, indolent CAFs, M2 macrophages, and bystander CD4+/CD8+ T cells. Significantly, customized therapies are proposed. For HRD patients, targeting FGFR1+PDGFRß+ myCAFs via tyrosine kinase inhibitors, targeting Tregs via anti-CCR8 antibodies/TNFRSF4 stimulation, and targeting CXCL13+ exhausted T cells by blocking PDCD1/CTLA-4/LAG-3/TIGIT are proposed. For HRP patients, targeting indolent CAFs, targeting M2 macrophages via CSF-1/CSF-1R inhibitors, targeting bystander T cells via tumor vaccines, and targeting epithelial cells via HDAC inhibitors. The study provides comprehensive insights into HRD and HRP TIME and tailored therapeutic approaches, addressing the challenges of PARPi-resistant HRD and refractory HRP tumors.
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Objective: This study aimed to investigate the role of acellular amniotic membrane (AAM) loaded with adipose-derived mesenchymal stem cells (ADSCs) for the treatment of intrauterine adhesion. Methods: One hundred twenty female Spargue-Dawley rats were randomly divided into four groups: sham operation group (the uterus was picked out and incised without treatment), intrauterine adhesion group, the experimental group treated with AAM, and experimental group treated with AAM loaded with ADSCs. Histological and immunohistochemical analysis were performed on 3, 7, and 14 days after surgery to evaluate the degree of uterine fibrosis and regeneration of injured endometrium. RNA sequencing and real-time PCR were used to explore the potential mechanism by which ADSCs modulated immune response and promoted endometrial regeneration. Results: On 14 days after surgery, the endometrial thickness, number of glands, and degree of fibrosis reduction in the ADSCs/AAM group was higher than those in the AAM group, and similar to the sham operation group. RNA sequencing analysis showed that ADSCs can modulate local immune responses and promote the formation of functional endometrium. Meanwhile, we found that ADSCs significantly decreased the levels of pro-inflammatory cytokines (TNF-α and IL-1ß) and increased the levels of anti-inflammatory cytokines (bFGF and IL-6). Conclusion: Our results demonstrated that AAM loaded with ADSCs can result in the regeneration of injured endometrium and fibrosis reduction. Meanwhile, ADSCs also regulated the immune microenvironment, which was beneficial to functional endometrial recovery.
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BACKGROUND: The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare condition with significant psychological implications. However, our understanding of its impact on postoperative sexual function and mental health is still limited. AIM: Evaluate the mental health status and sexual functioning of women with MRKH syndrome after vaginoplasty surgery. METHODS: We enrolled 53 cases with MRKH syndrome who underwent artificial vaginoplasty. The participants were asked to participate in a two-round survey conducted between February 2021 during the covid-19 period and March 2023. The survey included questionnaires to measure depression, anxiety, self-esteem, and sexual functioning. Differences between scores over time were analysed using a paired sample t-test, and we assessed the correlation between mental health and sexual functioning. RESULTS: In the first round, patients' mean ± SD age at surgery was 23.6 ± 4.5 years old, and the mean ± SD time that had elapsed since surgery at the time of the survey was 34.2 ± 20.8 months. None of the patients reported low self-esteem, 45.3 % reported mild-to-moderate depression, and 34.0 % reported mild anxiety. Thirty patients have had vaginal intercourse during the last six months. The mean ± SD Female Sexual Functioning Index score was 24.6 ± 4.4, and 60.0 % had a score of 23.5 or higher, indicating high sexual functioning. The sexual functioning scores were positively correlated with self-esteem scores and negatively correlated with depression or anxiety scores (p < 0.05). There was no significant improvement in patient's mental health status and sexual function between the second round survey (71.3 ± 17.8 months after surgery) and the first round survey (p > 0.05). In contrast, the sexual arousal of FSFI were significantly higher in the second survey round (p < 0.05). CONCLUSION: Most patients undergoing vaginoplasty reported persisting mental health challenges. However, the majority reported good sexual functioning.
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Transtornos 46, XX do Desenvolvimento Sexual , Ansiedade , Anormalidades Congênitas , Depressão , Ductos Paramesonéfricos , Autoimagem , Vagina , Humanos , Feminino , Transtornos 46, XX do Desenvolvimento Sexual/cirurgia , Transtornos 46, XX do Desenvolvimento Sexual/psicologia , Vagina/cirurgia , Vagina/anormalidades , Ductos Paramesonéfricos/anormalidades , Ductos Paramesonéfricos/cirurgia , Anormalidades Congênitas/cirurgia , Anormalidades Congênitas/psicologia , Adulto , Depressão/psicologia , Depressão/etiologia , Ansiedade/psicologia , Ansiedade/etiologia , Adulto Jovem , Comportamento Sexual/psicologia , Adolescente , COVID-19/psicologiaRESUMO
Cervical cancer is a severe threat to women's health worldwide with a long cancerous cycle and a clear etiology, making early screening vital for the prevention and treatment. Based on the dataset provided by the Obstetrics and Gynecology Hospital of Fudan University, a four-category classification model for cervical lesions including Normal, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and cancer (Ca) is developed. Considering the dataset characteristics, to fully utilize the research data and ensure the dataset size, the model inputs include original and acetic colposcopy images, lesion segmentation masks, human papillomavirus (HPV), thinprep cytologic test (TCT) and age, but exclude iodine images that have a significant overlap with lesions under acetic images. Firstly, the change information between original and acetic images is introduced by calculating the acetowhite opacity to mine the correlation between the acetowhite thickness and lesion grades. Secondly, the lesion segmentation masks are utilized to introduce prior knowledge of lesion location and shape into the classification model. Lastly, a cross-modal feature fusion module based on the self-attention mechanism is utilized to fuse image information with clinical text information, revealing the features correlation. Based on the dataset used in this study, the proposed model is comprehensively compared with five excellent models over the past three years, demonstrating that the proposed model has superior classification performance and a better balance between performance and complexity. The modules ablation experiments further prove that each proposed improved module can independently improve the model performance.
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Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologia , Interpretação de Imagem Assistida por Computador/métodos , Colo do Útero/diagnóstico por imagem , Colo do Útero/patologia , Adulto , Colposcopia/métodosRESUMO
PD-1 blockade is a first-line treatment for recurrent/metastatic cervical cancer but benefits only a small number of patients due to low preexisting tumor immunogenicity. Using immunogenic cell death (ICD) inducers is a promising strategy for improving immunotherapy, but these compounds are limited by the hypoxic environment of solid tumors. To overcome this issue, the nanosensitizer AIBA@MSNs were designed based on sonodynamic therapy (SDT), which induces tumor cell death under hypoxic conditions through azo free radicals in a method of nonoxygen radicals. Mechanistically, the azo free radicals disrupt both the structure and function of tumor mitochondria by reversing the mitochondrial membrane potential and facilitating the collapse of electron transport chain complexes. More importantly, the AIBA@MSN-based SDT serves as an effective ICD inducer and improves the antitumor immune capacity. The combination of an AIBA@MSN-based SDT with a PD-1 blockade has the potential to improve response rates and provide protection against relapse. This study provides insights into the use of azo free radicals as a promising SDT strategy for cancer treatment and establishes a basic foundation for nonoxygen-dependent SDT-triggered immunotherapy in cervical cancer treatment.
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Imunoterapia , Neoplasias do Colo do Útero , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/imunologia , Feminino , Radicais Livres/química , Humanos , Camundongos , Animais , Compostos Azo/química , Compostos Azo/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Camundongos Endogâmicos BALB C , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacosRESUMO
[This corrects the article DOI: 10.3389/fimmu.2022.897366.].
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BACKGROUND: Several risk factors have been identified that compromise the treatment outcome in patients with early-to-mid-stage cervical cancer (CC) who are primarily treated with radical surgery. However, there is no report on the impact of intraoperative frozen pathology examination of vaginal margins on the prognosis of patients with CC. This study aimed to conduct a randomized controlled trial (RCT) to determine whether selective vaginal resection can reduce the incidence of operative complications and the risk of postoperative radiotherapy. The impact of the length of the vagina removed in radical hysterectomy (RH) on prognosis and quality of life (QoL) for IB2-IIA2 CC patients will be investigated. METHODS: A multicenter, non-inferiority, RCT at 7 institutions in China is designed to investigate the effect of intraoperative frozen pathology exam of vaginal margin in RH on the survival outcomes for patients with IB2-IIA2 CC. Eligible patients aged 18-70 years will be randomly assigned online by one-to-one random allocation to receive intraoperative frozen pathology exam of vaginal margin or not. If frozen pathology indicates positive margin, continue resection of 1 centimeter of vaginal tissue until negative margin is achieved. The primary end point is 2-year disease-free survival (DFS). Adverse events (AEs) caused by further vagina resection, 5-year DFS, 2-year overall survival (OS), 5-year OS and AEs caused by radiotherapy and QoL are secondary end points. A total of 310 patients will be enrolled from 7 tertiary hospitals in China within 3-year period and followed up for 5 years. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR2000035668.
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Secções Congeladas , Histerectomia , Margens de Excisão , Qualidade de Vida , Neoplasias do Colo do Útero , Adolescente , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , China/epidemiologia , Intervalo Livre de Doença , Histerectomia/métodos , Estadiamento de Neoplasias , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Vagina/patologia , Vagina/cirurgia , Estudos Multicêntricos como AssuntoRESUMO
Objective: Due to the information-rich nature of positron emission tomography/computed tomography (PET/CT) images, the authors hope to explore radiomics features that could distinguish metastatic lymph nodes (LNs) from hypermetabolic benign LNs, in addition to conventional indicators. Methods: PET/CT images of 106 patients with early-stage cervical cancer from 2019 to 2021 were retrospectively analyzed. The tumor lesions and LN regions of PET/CT images were outlined with SeeIt, and then radiomics features were extracted. The least absolute shrinkage and selection operator (LASSO) was used to select features. The final selected radiomics features of LNs were used as predictors to construct a machine learning model to predict LN metastasis. Results: The authors determined two morphological coefficient characteristics of cervical lesions (shape - major axis length and shape - mesh volume), one first order characteristics of LNs (first order - 10 percentile) and two gray-level co-occurrence matrix (GLCM) characteristics of LNs (GLCM - id and GLCM - inverse variance) were closely related to LN metastasis. Finally, a neural network was constructed based on the radiomic features of the LNs. The area under the curve of receiver operating characteristic (AUC-ROC) of the model was 0.983 in the training set and 0.860 in the test set. Conclusion: The authors constructed and demonstrated a neural network based on radiomics features of PET/CT to evaluate the risk of single LN metastasis in early-stage cervical cancer.
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BACKGROUND: To introduce a novel technique of transvaginal extraperitoneal single-port laparoscopic sacrocolpopexy (ESLS) for apical prolapse and to evaluate the feasibility and short-term outcomes of this technique. METHODS: Sixteen patients were enrolled to undergo ESLS between January 2020 and May 2021. Perioperative outcomes were included. Short-term results were assessed by Pelvic Floor Distress Inventory-20 (PFDI-20), Pelvic Organ Prolapse Quantification (POP-Q) scores, mesh exposure and prolapse recurrence. RESULTS: A total of 14/16 cases (87.5%) were successfully completed. The mean operation time was 118 min (range 85-160), and the mean blood loss was 68 ml (range 20-100). The mean postoperative visual analog scale (VAS) pain score at 24 h was 0.7. No intraoperative complications occurred except for one patient who developed subcutaneous emphysema. All patients gained a significant improvement in both physical prolapse and quality of life at 12 months after surgery, and there was no mesh exposure or prolapse recurrence. CONCLUSIONS: Our experience showed that transvaginal ESLS is a feasible and effective technique for apical prolapse with a previous hysterectomy. However, this technique should be performed by surgeons with extensive experience both in vaginal surgery and laparoscopic single-port surgery.
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Laparoscopia , Prolapso de Órgão Pélvico , Feminino , Humanos , Vagina/cirurgia , Qualidade de Vida , Histerectomia , Prolapso de Órgão Pélvico/cirurgia , Laparoscopia/métodos , China , Telas Cirúrgicas , Resultado do TratamentoRESUMO
In recent years, the ubiquitin-proteasome system (UPS) has become a hot spot in medical research in cervical cancer (CC) and has received extensive attention. Among them, ubiquitin-specific protease 14 (USP14) is involved in a wide variety of typical cell signaling pathways and is recognized to be involved in the progression of most known tumors. However, the expression and significance of USP14 in CC have not been directly studied. Through database analysis, we found that USP14 was overexpressed in CC, which influenced the FIGO stage and prognosis of CC patients, and it was positively correlated with the expression level of ß-catenin. In this study, USP14 promoted the G1-S phase transition of Hela and Siha cells and inhibited cell apoptosis, thereby promoting the proliferation, migration, and invasion of CC cells. In addition, USP14 also significantly promoted the growth of subcutaneous tumor in nude mice. We also found that overexpression of USP14 significantly upregulated ß-catenin expression and increased the activity of Wnt/ß-catenin signaling pathway. While knockdown of USP14 resulted in the opposite. These results suggest that USP14 may promote the proliferation of CC by up-regulating the expression of ß-catenin, contributing to a deeper understanding of the mechanisms of CC and providing a potential therapeutic target.
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Neoplasias do Colo do Útero , beta Catenina , Animais , Feminino , Humanos , Camundongos , beta Catenina/genética , beta Catenina/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Neoplasias do Colo do Útero/metabolismo , Via de Sinalização WntRESUMO
OBJECTIVE: This study aims to describe cervical cancer during pregnancy (CCP) and investigate factors associated with survival outcomes. METHODS: This retrospective matched study included CCP patients from May 2007 to August 2021 and matched non-pregnant cervical cancer patients (1:2) based on age (±5 years), year at diagnosis (±2 years), histological type and stage (2018 FIGO). The Kaplan-Meier method and multivariate Cox regression analyses were used to assess the impact of pregnancy and clinicopathologic factors on prognosis. RESULTS: Thirty-eight CCP patients (stage IA to IIIC) and 76 non-pregnant patients were included. Most CCP patients were diagnosed in the first (31.6%) or second (47.4%) trimester. CCP patients had a longer waiting time than non-pregnant patients. Pregnancy continued in 42.1% (continuation of pregnancy [COP] group) and was terminated in 57.9% (termination of pregnancy [TOP] group) of patients. Survival analysis showed no significant differences in recurrence-free survival (RFS) or overall survival (OS) between pregnant and non-pregnant patients or between the COP and TOP groups. At the end of the follow-up period (range 12-178 months), 23 children born to CCP patients exhibited normal development. CONCLUSION: Pregnancy does not impact cervical cancer prognosis. The oncologic outcomes of the TOP and COP groups were comparable. A pregnancy-preserving strategy could be considered for managing CCP patients.
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Complicações Neoplásicas na Gravidez , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/diagnóstico , Gravidez , Estudos Retrospectivos , Adulto , Complicações Neoplásicas na Gravidez/terapia , Complicações Neoplásicas na Gravidez/patologia , Complicações Neoplásicas na Gravidez/mortalidade , Estadiamento de Neoplasias , Prognóstico , Estimativa de Kaplan-Meier , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: Radical hysterectomy (RH) is commonly used to treat early-stage cervical cancer in women of childbearing age and sexual dysfunction due to postoperative vaginal shortening is a major concern. The impact of intraoperative vaginoplasty on prognosis and quality of sexual life in patients with early-stage cervical cancer remains controversial and lacks high-level evidence. However, there are few reports on vaginoplasty after RH to lengthen vagina in patients. This prospective, multi-center, randomized controlled trial aims to explore the impact of peritoneal vaginoplasty with or without ovarian transposition after laparoscopic RH on sexual dysfunction in patients with early-stage cervical cancer. METHODS: Eligible patients will be randomly assigned (1:1) to receive peritoneal vaginoplasty or not. The primary evaluation indicators are female sexual function index (FSFI) and male sexual satisfaction scale. The secondary evaluation indicators include EORTC QLQ-CX24, 2-year overall survival (OS), 5-year OS, 2-year progression-free survival (PFS), 5-year PFS and surgery-related complications. The trial will enroll 368 patients from 6 hospitals in China over a 3-year period and follow up for 5 years. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR2000040610.
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Background: Radical hysterectomy (RH) is considered a cornerstone in the treatment of early-stage cervical cancer. However, the debate surrounding the optimal surgical approach, whether minimally invasive or open surgery, remains controversial. The objective of this trial is to evaluate the survival outcomes of cervical cancer patients who undergo different surgical approaches. Methods: This study is designed as a prospective, multicenter, open, parallel, and randomized controlled trial. A total of 500 patients diagnosed with stage IA1 with LVSI, IA2, IB1, or IB2 (2018 FIGO) will be recruited. Recruitment of participants started in November 2020. The participants will be randomly assigned to one of three groups: conventional laparoscopic RH, gasless laparoscopic RH, or abdominal RH. The primary endpoint of this trial is the 2-year disease-free survival (DFS) rate. The secondary endpoints will include the 2-year overall survival (OS) rate, 5-year DFS/OS, recurrence rates, operation time, intraoperative blood loss, surgery-related complications, and impact on quality of life (QoL). Discussion: We expect this trial to provide compelling and high-quality evidence to guide the selection of the most appropriate surgical approach for early-stage cervical cancer. Clinical trial registration: Chinese Clinical Trial Register, identifier ChiCTR2000035515.
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BACKGROUND: Cervical cancer (CC) is the fourth most common cancer in women worldwide. Although immunotherapy has been applied in clinical practice, its therapeutic efficacy remains far from satisfactory, necessitating further investigation of the mechanism of CC immune remodeling and exploration of novel treatment targets. This study aimed to investigate the mechanism of CC immune remodeling and explore potential therapeutic targets. METHODS: We conducted single-cell RNA sequencing on a total of 17 clinical specimens, including normal cervical tissues, high-grade squamous intraepithelial lesions, and CC tissues. To validate our findings, we conducted multicolor immunohistochemical staining of CC tissues and constructed a subcutaneous tumorigenesis model in C57BL/6 mice using murine CC cell lines (TC1) to evaluate the effectiveness of combination therapy involving indoleamine 2,3-dioxygenase 1 (IDO1) inhibition and immune checkpoint blockade (ICB). We used the unpaired two-tailed Student's t-test, Mann-Whitney test, or Kruskal-Wallis test to compare continuous data between two groups and one-way ANOVA with Tukey's post hoc test to compare data between multiple groups. RESULTS: Malignant cervical epithelial cells did not manifest noticeable signs of tumor escape, whereas lysosomal-associated membrane protein 3-positive (LAMP3+ ) dendritic cells (DCs) in a mature state with immunoregulatory roles were found to express IDO1 and affect tryptophan metabolism. These cells interacted with both tumor-reactive exhausted CD8+ T cells and CD4+ regulatory T cells, synergistically forming a vicious immunosuppressive cycle and mediating CC immune escape. Further validation through multicolor immunohistochemical staining showed co-localization of neoantigen-reactive T cells (CD3+ , CD4+ /CD8+ , and PD-1+ ) and LAMP3+ DCs (CD80+ and PD-L1+ ). Additionally, a combination of the IDO1 inhibitor with an ICB agent significantly reduced tumor volume in the mouse model of CC compared with an ICB agent alone. CONCLUSIONS: Our study suggested that a combination treatment consisting of targeting IDO1 and ICB agent could improve the therapeutic efficacy of current CC immunotherapies. Additionally, our results provided crucial insights for designing drugs and conducting future clinical trials for CC.
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Linfócitos T Reguladores , Neoplasias do Colo do Útero , Animais , Feminino , Humanos , Camundongos , Linfócitos T CD8-Positivos/metabolismo , Células Dendríticas , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Proteínas de Membrana Lisossomal/metabolismo , Camundongos Endogâmicos C57BL , Proteínas de Neoplasias/metabolismo , Linfócitos T Reguladores/metabolismo , Microambiente Tumoral , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/metabolismoRESUMO
This study aimed to investigate whether CKAP2 could promote cervical cancer (CC) progression by modulating the tumor microenvironment (TME) via NF-κB signaling. The communication between cervical cancer cells and the TME, including THP-1 and HUVECs, was tested. Gain- and loss-of-function assays were performed to elucidate the role of CKAP2 in cervical cancer progression. Western blot analysis was exploited to investigate the potential involved mechanism involved. Here, we reported that cervical cancer tissues were enriched with macrophages and microvessels. CKAP2 increased the tumor-promoting macrophage population. The overexpression of CKAP2 not only promoted endothelial cell viability and tube formation but also increased vascular permeability, and vice versa. Moreover, CKAP2 promoted cervical cancer progression via NF-κB signaling. This effect could be blocked by the NF-κB signaling inhibitor JSH-23. Our findings indicated that CKAP2 could promote cervical cancer progression by modulating the TME via NF-κB signaling.
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Long noncoding RNAs (lncRNAs) represent a class of versatile molecules that exhibit the potential to regulate gene expression at various levels, namely transcriptional, posttranscriptional and epigenetic, thereby influencing critical cellular processes such as proliferation, apoptosis, invasion and drug resistance. The lncRNA H19, among the earliest identified within this category, has emerged as a significant participant in the pathogenesis of a multitude of both malignant and benign gynecological diseases. An escalating body of evidence indicates a functionally pertinent network of lncRNA H19 coexpression linked with the extracellular matrix architecture and immune microenvironment during cancer progression. This association may provide insightful leads for the selection of innovative diagnostic biomarkers and assist in the delineation of potent pharmaceutical targets for gynecological oncology. The present comprehensive review presented a synthesis of the expression profiles and multifaceted implications of lncRNA H19 across a spectrum of gynecological pathologies.
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RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Regulação da Expressão Gênica , Genes Supressores de Tumor , Proliferação de Células/genética , Regulação Neoplásica da Expressão GênicaRESUMO
CD24 is a glycosylphosphatidylinositol linked molecular which expressed in diverse malignant tumor cells, particular in ovarian carcinoma cells and ovarian carcinoma stem cells. The CD24 expression is associated with increased metastatic potential and poor prognosis of malignancies. CD24 on the surface of tumor cells could interact with Siglec-10 on the surface of immune cells, to mediate the immune escape of tumor cells. Nowadays, CD24 has been identified as a promising focus for targeting therapy of ovarian cancer. However, the roles of CD24 in tumorigenesis, metastasis, and immune escape are still not clearly demonstrated systematically. In this review, we i) summarized the existing studies on CD24 in diverse cancers including ovarian cancer, ii) illustrated the role of CD24-siglec10 signaling pathway in immune escape, iii) reviewed the existing immunotherapeutic strategies (targeting the CD24 to restore the phagocytic effect of Siglec-10 expressing immune cells) based on the above mechanisms and evaluated the priorities in the future research. These results might provide support for guiding the CD24 immunotherapy as the intervention upon solid tumors.
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Carcinoma , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/metabolismo , Carcinoma Epitelial do Ovário , Transdução de Sinais , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/metabolismo , Antígeno CD24/metabolismoRESUMO
BACKGROUND: At present, clinical dilemma remains to be solved in terms of therapy-choices for specific locally advanced cervical cancer (LACC) patients: 1) Although concurrent chemoradiotherapy (CCRT) is recommended as the first choice for them, many patients, influenced by the Chinese culture, prefer to choose radical surgery (RS) as their primary treatment. The difference between the 2 therapies in improving patient prognosis is still unknown. 2) Laparoscopy has been questioned since the noted Laparoscopic Approach to Cervical Cancer trial. Nevertheless, clinical research on laparoscopic surgery under the strict tumor-free principle is still underway globally, therefore whether laparoscopic surgery can be used for specific LACC is also an urgent issue to be explored. METHODS: A multi-center, randomized controlled study is designed to investigate the effect of different treatment strategies on the prognosis and quality of life (QoL) in patients with specific locally LACC. A total of 402 patients will be enrolled over a period of 3 years. Eligible patients will be randomized (3:1) to either RS group or CCRT group. Patients assigned to RS group will be randomized (1:2) to the abdominal RS group or laparoscopic RS group. All patients will then be followed-up for 5 years. The primary end point is the 2-year progression-free survival (PFS). The secondary end points include 5-year PFS, 2-year overall survival (OS), 5-year OS, adverse events caused by RS or CCRT and QoL. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR2000041315.
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Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/patologia , Qualidade de Vida , Quimiorradioterapia/métodos , Carcinoma de Células Escamosas/patologia , Adenocarcinoma/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
Cervical squamous cell carcinoma (SCC) and adenocarcinoma (AD) are the main histological types of human papillomavirus-related cervical cancer. However, there are few reports on cell type-specific molecular differences between SCC and AD. Here, we used unbiased droplet-based single-cell RNA sequencing to elucidate the cellular differences between SCC and AD in tumor heterogeneity, and tumor microenvironment (TME). A total of 61 723 cells from three SCC and three AD patients, were collected and divided into nine cell types. Epithelial cells exhibited high intra- and interpatient heterogeneity and functional diversity. Signaling pathways, such as epithelial-to-mesenchymal-transition (EMT), hypoxia and inflammatory response were upregulated in SCC, while cell cycle-related signaling pathways were highly enriched in AD. SCC was associated with high infiltration of cytotoxicity CD8 T, effector memory CD8 T, proliferative natural killer (NK), and CD160+ NK cells as well as tumor-associated macrophages (TAMs) with high major histocompatibility complex-II genes. AD exhibited a high proportion of naive CD8 T, naive CD4 T, Treg CD4, central memory CD8, and TAMs with immunomodulatory functions. Additionally, we also observed that the majority of cancer-associated fibroblasts (CAFs) were from AD, and participated in inflammation regulation, while SCC-derived CAFs exhibited similar functions to tumor cells, such as EMT and hypoxia. This study revealed the widespread reprogramming of multiple cell populations in SCC and AD, dissected the cellular heterogeneity and characteristics in TME, and proposed potential therapeutic strategies for CC, such as targeted therapy and immunotherapy.