-
Asian Pacific Journal of Cancer... Jun 2024Nasopharyngeal carcinoma (NPC) is a common type of cancer in Southeast Asia. This cancer usually spreads locally and to nearby lymph nodes. One unique feature of NPC is...
BACKGROUND
Nasopharyngeal carcinoma (NPC) is a common type of cancer in Southeast Asia. This cancer usually spreads locally and to nearby lymph nodes. One unique feature of NPC is its many immune cells called tumor-infiltrating lymphocytes (TILs). Recent studies have suggested that TILs in many types of cancer can indicate a better prognosis. However, the role of TILs in NPC is still a matter of debate. Further research is necessary to determine whether TILs can be used as a prognostic factor of NPC's outcome.
METHOD
A retrospective cohort study was conducted at Sardjito Hospital to examine the records and pathological sections of patients treated for the undifferentiated subtype of NPC. Two pathologists analyzed the presence of TILs using HE-stained slides. TILs were evaluated in stromal compartments, and their association with clinicopathological variables was analyzed using the Chi-square and Fisher exact tests. The study compared overall survival in tumor patients with varying TIL levels using Kaplan-Meier survival curves and the log-rank test. A Cox regression model was used for univariate and multivariate analyses to test the significance of different factors.
RESULT
Out of the total 61 subjects, 16 (26.2%) had high stromal TILs (≥ 70%), and 45 (73.8%) had low stromal TILs (<70%). The subjects' sex, age, and tumor stage did not affect the OS. However, high stromal TILs (≥ 70%) showed a significant association with a longer OS (log-rank test p = 0.006, HR 0.37, 95% CI 0.17-0.79, log-rank p = 0.006). Moreover, multivariate analysis confirmed that TILs were an independent prognostic indicator for OS (aHR 0.015).
CONCLUSION
TILs correlate positively with overall survival in the undifferentiated NPC subtype and are an independent prognostic indicator.
Topics: Humans; Lymphocytes, Tumor-Infiltrating; Male; Female; Prognosis; Retrospective Studies; Nasopharyngeal Neoplasms; Middle Aged; Nasopharyngeal Carcinoma; Survival Rate; Adult; Carcinoma; Follow-Up Studies; Aged; Neoplasm Staging
PubMed: 38918661
DOI: 10.31557/APJCP.2024.25.6.1997 -
Medical Oncology (Northwood, London,... Jun 2024Glioblastoma (GBM) is the most common malignant brain tumor, which, despite significant progress made in the last years in the field of neuro-oncology, remains an... (Review)
Review
Glioblastoma (GBM) is the most common malignant brain tumor, which, despite significant progress made in the last years in the field of neuro-oncology, remains an incurable disease. GBM has a poor prognosis with a median survival of 12-15 months, and its aggressive clinical course is related to rapid growth, extensive infiltration of adjacent tissues, resistance to chemotherapy, radiotherapy and immunotherapy, and frequent relapse. Currently, several molecular biomarkers are used in clinical practice to predict patient prognosis and response to treatment. However, due to the overall unsatisfactory efficacy of standard multimodal treatment and the remaining poor prognosis, there is an urgent need for new biomarkers and therapeutic strategies for GBM. Recent evidence suggests that GBM tumorigenesis is associated with crosstalk between cancer, immune and stromal cells mediated by various cytokines. One of the key factors involved in this process appears to be interleukin-17 (IL-17), a pro-inflammatory cytokine that is significantly upregulated in the serum and tissue of GBM patients. IL-17 plays a key role in tumorigenesis, angiogenesis, and recurrence of GBM by activating pro-oncogenic signaling pathways and promoting cell survival, proliferation, and invasion. IL-17 facilitates the immunomodulation of the tumor microenvironment by promoting immune cells infiltration and cytokine secretion. In this article we review the latest scientific reports to provide an update on the role of IL-17 role in tumorigenesis, tumor microenvironment, diagnosis, prognosis, and treatment of GBM.
Topics: Humans; Glioblastoma; Brain Neoplasms; Interleukin-17; Tumor Microenvironment; Biomarkers, Tumor; Prognosis
PubMed: 38918274
DOI: 10.1007/s12032-024-02434-1 -
Journal of Cancer Research and Clinical... Jun 2024Hepatocellular carcinoma (HCC) is a critical global health concern, with existing treatments benefiting only a minority of patients. Recent findings implicate the...
PURPOSE
Hepatocellular carcinoma (HCC) is a critical global health concern, with existing treatments benefiting only a minority of patients. Recent findings implicate the chemokine ligand 17 (CCL17) and its receptor CCR4 as pivotal players in the tumor microenvironment (TME) of various cancers. This investigation aims to delineate the roles of CCL17 and CCR4 in modulating the tumor's immune landscape, assessing their potential as therapeutic interventions and prognostic markers in HCC.
METHODS
873 HCC patients post-radical surgery from 2008 to 2012 at Zhongshan Hospital, Fudan University were retrospectively examined. These individuals were stratified into a training cohort (n = 354) and a validation cohort (n = 519). Through immunohistochemical analysis on HCC tissue arrays, the expressions of CCL17, CCR4, CD73, CD47, HHLA2, and PD-L1 were quantified. Survival metrics were analyzed using the Cox model, and a prognostic nomogram was devised via R software.
RESULTS
The investigation confirmed the presence of CCL17 and CCR4 within the cancerous and stromal compartments of HCC tissues, associating their heightened expression with adverse clinical markers and survival outcomes. Notably, the interplay between CD73 and CCR4 expression in tumor stroma highlighted a novel cellular entity, CCR4 + CD73 + stromal cells, impacting overall and relapse-free survival. A prognostic nomogram amalgamating these immunological markers and clinical variables was established, offering refined prognostic insights and aiding in the management of HCC. The findings suggest that reduced CCR4 and CCR4 + CD73 + cell prevalence may forecast improved outcomes post-TACE.
CONCLUSION
This comprehensive evaluation of CCR4, CCL17, and associated markers introduces a nuanced understanding of the HCC immunological milieu, proposing CCR4 + CD73 + stromal cells as critical to HCC pathogenesis and patient stratification.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Chemokine CCL17; Female; Male; Prognosis; Receptors, CCR4; Middle Aged; Biomarkers, Tumor; 5'-Nucleotidase; Retrospective Studies; Tumor Microenvironment; GPI-Linked Proteins; Aged; Adult
PubMed: 38914802
DOI: 10.1007/s00432-024-05832-0 -
Journal of Applied Biomedicine Jun 2024Diffuse large B-cell lymphoma (DLBCL) stands out as the most common type of malignant cancer, representing the majority of cases of non-Hodgkin's lymphoma. Ethyl...
Diffuse large B-cell lymphoma (DLBCL) stands out as the most common type of malignant cancer, representing the majority of cases of non-Hodgkin's lymphoma. Ethyl pyruvate (EP) is a derivative of pyruvic acid and found to have potent anti-tumor properties. Despite its potential benefits, the impact of EP on DLBCL remains ambiguous. Our objective is to elucidate the role of EP in modulating the development of DLBCL. Analysis of cholecystokinin-8 (CCK-8) revealed that treatment with EP significantly diminished the viability of DLBCL cells. Furthermore, EP administration suppressed colony formation and hindered cell adhesion and invasion in DLBCL cells. Examination of cell cycle progression showed that EP treatment induced arrest at the G1 phase and subsequently reduced the S phase population in DLBCL cells. EP treatment consistently exhibited apoptosis-inducing properties in Annexin-V assays, and notably downregulated the expression of Bcl-2 while increasing levels of proapoptotic cleaved caspase 3 and BAX in DLBCL cells. Additionally, EP treatment decreased the overexpression of c-Jun in c-Jun-transfected DLBCL cells. Further, EP demonstrated DNA-damaging effects in TUNEL assays. In vivo, xenograft animal models revealed that EP treatment significantly mitigated DLBCL tumor growth and suppressed DLBCL cell adhesion to bone marrow stromal cells. In summary, these findings suggest that EP mitigates DLBCL progression by inducing apoptosis, inducing cell cycle arrest, and promoting DNA damage.
Topics: Pyruvates; Lymphoma, Large B-Cell, Diffuse; Humans; Animals; Cell Adhesion; Cell Proliferation; Cell Line, Tumor; Mice; Apoptosis; Proto-Oncogene Proteins c-jun; Xenograft Model Antitumor Assays
PubMed: 38912866
DOI: 10.32725/jab.2024.014 -
International Journal of Nanomedicine 2024The tumor microenvironment (TME) is a complex and dynamic entity, comprising stromal cells, immune cells, blood vessels and extracellular matrix, which is intimately... (Review)
Review
The tumor microenvironment (TME) is a complex and dynamic entity, comprising stromal cells, immune cells, blood vessels and extracellular matrix, which is intimately associated with the occurrence and development of cancers, as well as their therapy. Utilizing the shared characteristics of tumors, such as an acidic environment, enzymes and hypoxia, researchers have developed a promising cancer therapy strategy known as responsive release of nano-loaded drugs, specifically targeted at tumor tissues or cells. In this comprehensive review, we provide an in-depth overview of the current fundamentals and state-of-the-art intelligent strategies of TME-responsive nanoplatforms, which include acidic pH, high GSH levels, high-level adenosine triphosphate, overexpressed enzymes, hypoxia and reductive environment. Additionally, we showcase the latest advancements in TME-responsive nanoparticles. In conclusion, we thoroughly examine the immediate challenges and prospects of TME-responsive nanopharmaceuticals, with the expectation that the progress of these targeted nanoformulations will enable the exploitation, overcoming or modulation of the TME, ultimately leading to significantly more effective cancer therapy.
Topics: Tumor Microenvironment; Humans; Neoplasms; Nanoparticles; Drug Delivery Systems; Antineoplastic Agents; Animals; Hydrogen-Ion Concentration
PubMed: 38911497
DOI: 10.2147/IJN.S459710 -
BMC Women's Health Jun 2024This study aimed to evaluate the outcomes of patients diagnosed with stage IB2/IIA2 cervical squamous cell carcinoma who underwent neoadjuvant chemotherapy (NACT) prior...
BACKGROUND
This study aimed to evaluate the outcomes of patients diagnosed with stage IB2/IIA2 cervical squamous cell carcinoma who underwent neoadjuvant chemotherapy (NACT) prior to radical hysterectomy compared to those who did not receive NACT before surgery.
MATERIALS AND METHODS
This is a multicenter study including data of 6 gynecological oncology departments. The study is approved from one of the institution's local ethics committee. Patients were stratified into two cohorts based on the receipt of NACT preceding their surgical intervention. Clinico-pathological factors and progression-free survival were analyzed.
RESULTS
Totally 87 patients were included. Lymphovascular space invasion (LVSI) was observed as 40% in the group receiving NACT, while it was 66.1% in the group not receiving NACT (p = 0.036). Deep stromal invasion (> 50%) was 56% in the group receiving NACT and 84.8% in the group not receiving NACT (p = 0.001). In the univariate analysis, application of NACT is statistically significant among the factors that would be associated with disease-free survival. Consequently, a multivariate analysis was conducted for progression-free survival, incorporating factors such as the depth of stromal invasion, the presence of LVSI, and the administration of NACT. Of these, only the administration of NACT emerged as an independent predictor associated with decreased progression-free survival. (RR:5.88; 95% CI: 1.63-21.25; p = 0.07).
CONCLUSIONS
NACT shouldn't be used routinely in patients with stage IB2/IIA2 cervical cancer before radical surgery. Presented as oral presentation at National Congress of Gynaecological Oncology & National Congress of Cervical Pathologies and Colposcopy (2022/ TURKEY).
Topics: Humans; Female; Uterine Cervical Neoplasms; Neoadjuvant Therapy; Middle Aged; Carcinoma, Squamous Cell; Hysterectomy; Neoplasm Staging; Adult; Chemotherapy, Adjuvant; Aged; Retrospective Studies; Disease-Free Survival
PubMed: 38909186
DOI: 10.1186/s12905-024-03215-8 -
Journal of Medical Case Reports Jun 2024Due to rarity of duodenal GISTs, clinicians have few information about its clinical features, diagnosis, management and prognosis. (Review)
Review
BACKGROUND
Due to rarity of duodenal GISTs, clinicians have few information about its clinical features, diagnosis, management and prognosis.
CASE REPORT
We report a case of promptly diagnosed duodenal GIST in a 61-year-old Egyptian man presented shocked with severe attack of hematemesis and melena. Upper gastroduodenal endoscopy was done and revealed a large ulcerating bleeding mass at first part of duodenum 4 hemo-clips were applied with good hemostasis. An exploratory laparotomy and distal gastrectomy, duodenectomy and gastrojejunostomy were performed. The morphology of the mass combined with immunohistochemistry was consistent with duodenal gastrointestinal stromal tumours (GISTs) of high risk type. The patient is on amatinib one tablet daily and he was well with no evidence of tumor recurrence.
CONCLUSION
despite being rare, emergency presentation with sudden severe, life-threatening hemorrhagic shock duodenal GISTs might be a cause of potentially lethal massive combined upper and lower gastrointestinal bleeding which is the key feature of this rare and challenging tumor.
Topics: Humans; Gastrointestinal Stromal Tumors; Male; Middle Aged; Gastrointestinal Hemorrhage; Duodenal Neoplasms; Shock, Hemorrhagic; Melena; Hematemesis; Gastrectomy
PubMed: 38907357
DOI: 10.1186/s13256-024-04597-x -
Frontiers in Immunology 2024Cancer-associated fibroblasts (CAFs) are the primary stromal cells found in tumor microenvironment, and display high plasticity and heterogeneity. By using single-cell...
BACKGROUND
Cancer-associated fibroblasts (CAFs) are the primary stromal cells found in tumor microenvironment, and display high plasticity and heterogeneity. By using single-cell RNA-seq technology, researchers have identified various subpopulations of CAFs, particularly highlighting a recently identified subpopulation termed antigen-presenting CAFs (apCAFs), which are largely unknown.
METHODS
We collected datasets from public databases for 9 different solid tumor types to analyze the role of apCAFs in the tumor microenvironment.
RESULTS
Our data revealed that apCAFs, likely originating mainly from normal fibroblast, are commonly found in different solid tumor types and generally are associated with anti-tumor effects. apCAFs may be associated with the activation of CD4+ effector T cells and potentially promote the survival of CD4+ effector T cells through the expression of C1Q molecules. Moreover, apCAFs exhibited highly enrichment of transcription factors RUNX3 and IKZF1, along with increased glycolytic metabolism.
CONCLUSIONS
Taken together, these findings offer novel insights into a deeper understanding of apCAFs and the potential therapeutic implications for apCAFs targeted immunotherapy in cancer.
Topics: Tumor Microenvironment; Cancer-Associated Fibroblasts; Humans; Single-Cell Analysis; Neoplasms; Gene Expression Regulation, Neoplastic; Gene Expression Profiling; Core Binding Factor Alpha 3 Subunit; Transcriptome
PubMed: 38903527
DOI: 10.3389/fimmu.2024.1372432 -
Pathology Oncology Research : POR 2024The desmoplastic reaction is considered a promising prognostic parameter for colorectal cancer. However, intermediate desmoplastic reaction is characterized by sizeable...
BACKGROUND
The desmoplastic reaction is considered a promising prognostic parameter for colorectal cancer. However, intermediate desmoplastic reaction is characterized by sizeable stromal heterogeneity, including both small amounts of keloid-like collagen (KC) in the fibrotic stroma and thick tufts of KC circumferentially surrounding cancer nests and occupying most of the fields of view. The present study aimed to evaluate the diagnostic and prognostic significance of KC histophenotyping with a quantitative visual assessment of its presence in the stroma of the invasive margin of TNM (The "tumor-node-metastasis" classification) stage II/III colorectal cancer (CRC).
METHODS AND RESULTS
175 resected tumors from patients with TNM stage II/III CRC were examined. Keloid-like collagen was assessed according to Ueno H. criteria. KC was assessed at the primary tumor invasive margin using Hematoxylin & Eosin and Masson's trichrome staining. The cut-off point for KC was examined using "the best cutoff approach by log-rank test." Using a cutoff point of 30%, we histologically divided fibrous stroma in the invasive area into two groups: "type A"-KC ≤ 0.3 and "type B"-KC>0.3. Type A stroma was observed in 48% of patients, type B-in 52%. The association between collagen amount and 5-year recurrence-free survival (5-RFS) was assessed using Cox regression analysis. Kaplan-Meier analysis and log-rank tests were used to assess the significance of survival analysis. Analysis of categorical variables showed that increased KC in CRC stroma predicted adverse outcomes for 5-RFS (hazard ratio [HR] = 3.143, 95%, confidence interval [CI] = 1.643-6.012, = 0.001). Moreover, in Kaplan-Meier analysis, the log-rank test showed that type B exhibited worse 5-RFS than type A ( = 0.000).
CONCLUSION
KC is an independent predictor of 5-year overall and RFS in patients with TNM stage II/III CRC treated with surgery, with worse survival rates when the amount of KC increases by >30%.
Topics: Humans; Colorectal Neoplasms; Male; Female; Prognosis; Middle Aged; Collagen; Aged; Extracellular Matrix; Keloid; Adult; Aged, 80 and over; Survival Rate; Follow-Up Studies
PubMed: 38903488
DOI: 10.3389/pore.2024.1611789 -
Scientific Reports Jun 2024Carcinogenesis and tumor proliferation are characterized by a complex interaction of cancer cells with the tumor microenvironment. In particular, a tumor-promoting...
Carcinogenesis and tumor proliferation are characterized by a complex interaction of cancer cells with the tumor microenvironment. In particular, a tumor-promoting effect can be assumed for the stroma and its fibroblasts. An influence of the immune system on non small cell lung cancer (NSCLC) is now also suspected. In our study, we examined 309 sections of squamous cell carcinoma (SCC), a subtype of NSCLC. We determined the cell densities and areas of the different tissues in SCC using the software QuPath. Spearman rank correlation showed a significant positive correlation between the different tumor cell densities and stromal cell densities, and between tumor cell densities and immune cell densities. Overall survival curves by the Kaplan-Meier method revealed a prominent negative curve in cases of low immune cell density. Based on our results, we can assume a positive influence of the tumor microenvironment, especially the stromal cells, on tumor proliferation in SCC. We have also revealed that low density of immune cells is prognostically unfavorable.
Topics: Humans; Lung Neoplasms; Carcinoma, Squamous Cell; Tumor Microenvironment; Male; Female; Aged; Prognosis; Middle Aged; Stromal Cells; Kaplan-Meier Estimate; Carcinoma, Non-Small-Cell Lung; Cell Count
PubMed: 38902361
DOI: 10.1038/s41598-024-64956-y