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Cancer Immunology, Immunotherapy : CII Jul 2024Γδ T cell infiltration into tumours usually correlates with improved patient outcome, but both tumour-promoting and tumoricidal effects of γδ T cells have been...
Γδ T cell infiltration into tumours usually correlates with improved patient outcome, but both tumour-promoting and tumoricidal effects of γδ T cells have been documented. Human γδ T cells can be divided into functionally distinct subsets based on T cell receptor (TCR) Vδ usage. Still, the contribution of these different subsets to tumour immunity remains elusive. Here, we provide a detailed γδ T cell profiling in colon tumours, using mass and flow cytometry, mRNA quantification, and TCR sequencing. δ chain usage in both the macroscopically unaffected colon mucosa and tumours varied considerably between patients, with substantial fractions of Vδ1, Vδ2, and non-Vδ1 Vδ2 cells. Sequencing of the Vδ complementarity-determining region 3 showed that almost all non-Vδ1 Vδ2 cells used Vδ3 and that tumour-infiltrating γδ clonotypes were unique for every patient. Non-Vδ1Vδ2 cells from colon tumours expressed several activation markers but few NK cell receptors and exhaustion markers. In addition, mRNA analyses showed that non-Vδ1 Vδ2 cells expressed several genes for proteins with tumour-promoting functions, such as neutrophil-recruiting chemokines, Galectin 3, and transforming growth factor-beta induced. In summary, our results show a large variation in γδ T cell subsets between individual tumours, and that Vδ3 cells make up a substantial proportion of γδ T cells in colon tumours. We suggest that individual γδ T cell composition in colon tumours may contribute to the balance between favourable and adverse immune responses, and thereby also patient outcome.
Topics: Humans; Receptors, Antigen, T-Cell, gamma-delta; Colonic Neoplasms; Adenocarcinoma; Phenotype; Female; Male; T-Lymphocyte Subsets; Aged; Middle Aged; Lymphocytes, Tumor-Infiltrating
PubMed: 38953978
DOI: 10.1007/s00262-024-03758-7 -
Oncotarget Jul 2024
Topics: Pancreatic Neoplasms; Humans; Adenocarcinoma; Drug Screening Assays, Antitumor; Antineoplastic Agents
PubMed: 38953899
DOI: 10.18632/oncotarget.28556 -
Oncotarget Jul 2024Single-agent TAS102 (trifluridine/tipiracil) and regorafenib are FDA-approved treatments for metastatic colorectal cancer (mCRC). We previously reported that regorafenib...
Regorafenib synergizes with TAS102 against multiple gastrointestinal cancers and overcomes cancer stemness, trifluridine-induced angiogenesis, ERK1/2 and STAT3 signaling regardless of KRAS or BRAF mutational status.
Single-agent TAS102 (trifluridine/tipiracil) and regorafenib are FDA-approved treatments for metastatic colorectal cancer (mCRC). We previously reported that regorafenib combined with a fluoropyrimidine can delay disease progression in clinical case reports of multidrug-resistant mCRC patients. We hypothesized that the combination of TAS102 and regorafenib may be active in CRC and other gastrointestinal (GI) cancers and may in the future provide a treatment option for patients with advanced GI cancer. We investigated the therapeutic effect of TAS102 in combination with regorafenib in preclinical studies employing cell culture, colonosphere assays that enrich for cancer stem cells, and . TAS102 in combination with regorafenib has synergistic activity against multiple GI cancers including colorectal and gastric cancer, but not liver cancer cells. TAS102 inhibits colonosphere formation and this effect is potentiated by regorafenib. anti-tumor effects of TAS102 plus regorafenib appear to be due to anti-proliferative effects, necrosis and angiogenesis inhibition. Growth inhibition by TAS102 plus regorafenib occurs in xenografted tumors regardless of p53, KRAS or BRAF mutations, although more potent tumor suppression was observed with wild-type p53. Regorafenib significantly inhibits TAS102-induced angiogenesis and microvessel density in xenografted tumors, as well inhibits TAS102-induced ERK1/2 activation regardless of RAS or BRAF status . TAS102 plus regorafenib is a synergistic drug combination in preclinical models of GI cancer, with regorafenib suppressing TAS102-induced increase in microvessel density and p-ERK as contributing mechanisms. The TAS102 plus regorafenib drug combination may be further tested in gastric and other GI cancers.
Topics: Humans; Trifluridine; Phenylurea Compounds; Animals; Pyridines; Drug Synergism; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Neovascularization, Pathologic; Xenograft Model Antitumor Assays; Neoplastic Stem Cells; Gastrointestinal Neoplasms; Uracil; Mice; STAT3 Transcription Factor; Thymine; Drug Combinations; Cell Line, Tumor; Pyrrolidines; Mutation; Antineoplastic Combined Chemotherapy Protocols; MAP Kinase Signaling System; Signal Transduction; Cell Proliferation; Angiogenesis
PubMed: 38953895
DOI: 10.18632/oncotarget.28602 -
The British Journal of Surgery Jul 2024
Topics: Humans; Peritoneal Neoplasms; Stomach Neoplasms; Cytoreduction Surgical Procedures; Hyperthermic Intraperitoneal Chemotherapy; Combined Modality Therapy
PubMed: 38953711
DOI: 10.1093/bjs/znae149 -
Journal of Medical Virology Jul 2024The genetic diversity of killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) genes influences the host's immune response to viral...
The genetic diversity of killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) genes influences the host's immune response to viral pathogens. This study aims to explore the impact of five single nucleotide polymorphisms (SNPs) in KIR3DL2 and HLA-A genes on hepatitis C virus (HCV) infection. A total of 2251 individuals were included in the case-control study. SNPs including KIR3DL2 rs11672983, rs3745902, rs1654644, and HLA-A rs3869062, rs12202296 were genotyped. By controlling various confounding factors using a modified logistic regression model, as well as incorporating stratified analysis, joint effects analysis, and multidimensional bioinformatics analysis, we analyzed the relationship between SNPs and HCV infection. The logistic regression analysis showed a correlation between KIR3DL2 rs11672983 AA, KIR3DL2 rs3745902 TT, and increased HCV susceptibility (p < 0.01). Stratified analysis indicated that KIR3DL2 rs1654644 and HLA-A rs3869062 also heightened HCV susceptibility in certain subgroups. A linear trend of rising HCV infection rates was observed when combining KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT (p = 0.007). Bioinformatics analysis suggested these SNPs' regulatory potential and their role in altering messenger RNA secondary structure, implying their functional relevance in HCV susceptibility. Our findings indicate that KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT are significantly associated with increased susceptibility to HCV infection.
Topics: Humans; Male; Polymorphism, Single Nucleotide; Female; Case-Control Studies; Hepatitis C; Middle Aged; Genetic Predisposition to Disease; Adult; Genotype; HLA-A Antigens; Hepacivirus; Receptors, KIR; Aged; Receptors, KIR3DL2
PubMed: 38953430
DOI: 10.1002/jmv.29776 -
Cancer Medicine Jul 2024Sarcopenic obesity (SO) in patients with gastrointestinal cancer is associated with a poor prognosis. We aimed to investigate the prognostic impact of SO in patients...
BACKGROUND
Sarcopenic obesity (SO) in patients with gastrointestinal cancer is associated with a poor prognosis. We aimed to investigate the prognostic impact of SO in patients with gastrointestinal cancer, as well as the diagnostic cut-off value of SO in patients with gastrointestinal cancer among Chinese population.
METHODS
We conducted a consecutive cohort study. Between January 2017 and January 2019, 289 patients diagnosed with gastrointestinal cancer were included in our study. Skeletal muscle area, total fat area, and subcutaneous fat area were measured by CT scan. All patients were followed up for 5 years. Receiver operating characteristic curves (ROC) were adopted to determine the cut-off values of visceral fat obesity for the prediction of sarcopenia. Based on the cut-off values, patients with sarcopenia combined with visceral fat obesity were divided into the SO group, and the others were divided into the non-sarcopenic obesity (NSO) group. Kaplan-Meier curves and univariate and multivariate Cox proportional hazard models were employed to explore the associations of body composition profiles with 5-year overall survival and disease-specific survival.
RESULTS
Obtained from Youden's Index for ROC for the prediction of 5-year survival, skeletal muscle mass index (SMI) ≤40.02 cm/m with VFA ≥ 126.30 cm in men and SMI ≤32.05 cm/m with VFA ≥72.42 cm in women indicate a risk of poor prognosis in patients diagnosed with gastrointestinal cancer. Patients with SO had poorer 5-year overall survival (OS) than patients with NSO (6.74% vs. 82.84%, p < 0.001), and poorer 5-year DFS (6.74% vs. 81.82%, p < 0.001). In multivariate analysis, we found that the long-term mortality risk was approximately 13-fold higher among patients in the SO group compared to those with no conditions.
CONCLUSIONS
Preoperative assessment of SO is useful not only for monitoring nutritional status but also for predicting 5-year OS in gastrointestinal cancer patients.
Topics: Humans; Sarcopenia; Male; Female; Gastrointestinal Neoplasms; Prognosis; Middle Aged; Obesity; Aged; Body Composition; ROC Curve; Muscle, Skeletal; Kaplan-Meier Estimate; Intra-Abdominal Fat
PubMed: 38953401
DOI: 10.1002/cam4.7452 -
Cancer Medicine Jul 2024Lenvatinib (LEN) and atezolizumab + bevacizumab (A + B) have drastically changed the treatment paradigm for advanced hepatocellular carcinoma (HCC). Before these... (Comparative Study)
Comparative Study
BACKGROUND
Lenvatinib (LEN) and atezolizumab + bevacizumab (A + B) have drastically changed the treatment paradigm for advanced hepatocellular carcinoma (HCC). Before these landmark trials, sorafenib (SOR) served as the standard first-line treatment for a decade. Our study aimed to assess the outcomes of HCC patients treated during the SOR era (2008-2018) in contrast to those in the post-SOR era (2018-2021), of which the predominant first-line treatments were LEN or A + B.
METHODS
Inclusion criteria of the study were all HCC patients in the Canadian province of Alberta who started first-line systemic therapy at cancer centers between 1 January 2008 and 31 December 2021. Survival outcomes, including overall survival (OS) and progression-free survival (PFS), along with clinician-assessed response rate (RR), were subject to retrospective analysis.
RESULTS
Of 372 total patients, 230 received treatment in the SOR era and 142 in the post-SOR era. The demographic and clinical characteristics for the SOR era and post-SOR era groups are as follows, respectively: the median age was 63 and 64 years, 80% and 81% were male, and 24% and 11% were of East Asian ethnicity. Before receiving systemic treatment, 40% and 33% received TACE, 7% and 9% received TARE, and 3% and 14% received SBRT in the two eras, respectively. In the post-SOR era, patients received A + B (23%), LEN (51%), and SOR (23%) as first-line treatment. There was a statistically significant improvement in RR (15% vs. 26%; p = 0.02), median PFS (3.8 months vs. 7.9 months; p < 0.0001), and median OS (9.8 months vs. 17.0 months; p < 0.0001).
CONCLUSIONS
In this retrospective multicenter real-world study, HCC patients treated in the post-SOR era, where LEN and A + B were commonly used first-line treatments, exhibited superior OS, PFS, and RR compared to patients treated in the SOR era. The findings of this study affirm the tangible progress achieved in the real world in enhancing outcomes for HCC patients through advancements in treatments over the past 15 years.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Quinolines; Phenylurea Compounds; Male; Female; Middle Aged; Sorafenib; Retrospective Studies; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Progression-Free Survival; Bevacizumab; Treatment Outcome; Immunotherapy
PubMed: 38953381
DOI: 10.1002/cam4.7415 -
Asian Journal of Endoscopic Surgery Jul 2024This study aims to prove the feasibility and safety of robotic gastrectomy using the hinotori™ Surgical Robot System (Medicaroid Corporation, Kobe, Japan).
BACKGROUND
This study aims to prove the feasibility and safety of robotic gastrectomy using the hinotori™ Surgical Robot System (Medicaroid Corporation, Kobe, Japan).
METHODS
We retrospectively enrolled the 16 patients who underwent gastrectomy by the hinotori™ Surgical Robot System for gastric cancer at our hospital between June 2023 and January 2024. Console surgeons performed almost all lymphadenectomies, including the clipping of vessels. Assistant surgeons supported the lymphadenectomy using vessel sealing devices and during reconstruction.
RESULTS
Thirteen patients were cStage I, one patient was cStage II, and two patients were cStage III. Distal gastrectomy, proximal gastrectomy, and total gastrectomy were performed in 11, 1, and 4 patients, respectively. D1+ and D2 lymphadenectomies were performed in 11 and 5 patients, respectively. Billroth-I, Billroth-II, Roux-en-Y, and esophagogastrostomy were performed in three, six, six, and one patients, respectively. The median operation time was 282 (245-338) min, and the median console time was 226 (185-266) min. The median blood loss was 28 (12-50) mL, and the median amylase levels in drainage fluid were 280 (148-377) U/L on postoperative day 1 and 74 (42-148) U/L on postoperative day 3. There was anastomotic leakage (Clavien-Dindo [CD] IIIa) in one patient who underwent proximal gastrectomy. The median postoperative hospital stay was 12.5 (12-14) days.
CONCLUSION
In this initial case series, the hinotori™ Surgical Robot System was found to be safe and feasible for patients with gastric cancer and is suggested to be appropriate for gastrectomy, including distal gastrectomy and total gastrectomy.
Topics: Humans; Gastrectomy; Robotic Surgical Procedures; Stomach Neoplasms; Female; Male; Aged; Middle Aged; Retrospective Studies; Feasibility Studies; Operative Time; Lymph Node Excision; Aged, 80 and over; Adult; Treatment Outcome
PubMed: 38953286
DOI: 10.1111/ases.13349 -
Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Jun 2024Intestinal mantle cell lymphoma complicated with intussusception is rare in clinical practice,lacking specific clinical manifestations.CT and colonoscopy are helpful for...
Intestinal mantle cell lymphoma complicated with intussusception is rare in clinical practice,lacking specific clinical manifestations.CT and colonoscopy are helpful for the diagnosis of this disease,which need to be distinguished from colorectal cancer,Crohn's disease,and other pathological subtypes of lymphoma.The diagnosis still needs to be confirmed by pathological examination.This paper reports a case of intestinal mantle cell lymphoma complicated with ileocecal intussusception in an adult,aiming to improve the clinical and imaging doctors' understanding of this disease.
Topics: Humans; Lymphoma, Mantle-Cell; Intussusception; Male; Ileal Diseases; Intestinal Neoplasms; Middle Aged; Ileocecal Valve
PubMed: 38953271
DOI: 10.3881/j.issn.1000-503X.15783 -
Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Jun 2024Long-term treatment of anemia involving frequent blood transfusions and intravenous iron administration increases the risks of hepatic iron overload and steatosis in the... (Review)
Review
Long-term treatment of anemia involving frequent blood transfusions and intravenous iron administration increases the risks of hepatic iron overload and steatosis in the patients undergoing hemodialysis.Pathological accumulation of iron damages hepatocytes,not only elevating the risks of progressive hepatic fibrosis and cirrhosis but also potentially accelerating the process of hepatic steatosis.Iron overload and steatosis may interact with each other,exacerbating liver damage and ultimately leading to further deterioration of hepatic fibrosis and cirrhosis.MRI characterized by non-invasiveness and high repeatability,enables the simultaneous quantitative assessment of hepatic iron and fat content,providing crucial information for early diagnosis and intervention of liver diseases.In recent years,researchers have achieved significant advances in the application of MRI in the diagnosis and treatment of liver diseases.MRI can accurately reflect the extent of hepatic iron overload and steatosis in patients and predict the risk of liver diseases.This article reviews the latest advances,challenges,and perspectives in the application of MRI in assessing hepatic iron overload and steatosis in the patients undergoing hemodialysis,aiming to offer valuable references for clinical practice.
Topics: Humans; Iron Overload; Magnetic Resonance Imaging; Renal Dialysis; Fatty Liver; Liver
PubMed: 38953270
DOI: 10.3881/j.issn.1000-503X.16066