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•DC-based immunotherapy is one of the most widely used methods for cancer immunotherapy.•DC therapy with miR-155-enriched texosomes efficiently induced anti-tumor responses and ...significantly improved survival and inhibited tumor growth in the murine model of colorectal cancer.
Nowadays, various strategies are considered to prime Dendritic cells (DCs) with tumor antigens. The tumor cell-derived exosomes are recognized as one of the most efficient strategies for achieving this purpose. In this regard, MicroRNA 155 (miR-155) is employed as one of the most prominent miRNAs, which play substantial roles in DCs maturation and IL-12 production. This study investigates the tumor growth suppression and antitumor effects of DCs primed with miR-155-enriched exosome on the BALB/c murine model of colorectal cancer induced by CT-26 cell lines.
Therefore, a holistic framework is proposed for the analysis procedure. In the first stage, miRNA-155 was electroporated into texosomes. In the second stage, bonemarrow-derived DCs were treated with miRNA-155 enriched texosomes. Then, antitumor properties of manipulated DC have been evaluated in the BALB/c mice model of colorectal cancer. After DC immunotherapy, several features have been assessed for each animal, including survival, body weight, tumor volume/size, histopathology, and serum cytokine levels. Also, flow cytometric evaluation has been performed for the spleen and the tumor tissue T-cell subsets.
The findings demonstrated that the primed DCs could significantly increase IL-12p70 and IFN-γ in serum and accelerate the differentiation, proliferation, and cytotoxicity effects on the Th and CTL cells. Also, the treatment also increased the infiltration of Th and CTL cells into the tumor microenvironment while decreasing Tregs. This situation causes tumor growth control, and survival improvement.
Therefore, DC immunotherapywith miR-155-enriched texosomes can be employed as a the desired approach for inducing antitumor immune responses, controlling tumor growth, and improving survival in mice with colorectal cancer. However, it is essential to perform more investigations to confirm the clinical application of this approach in humans and other types of tumors.
Since the publication of MA-20 and EORTC-22922 trials, chest wall (CW)/ whole breast (WB) irradiation + comprehensive regional nodal irradiation (RNI) with internal mammary node irradiation (IMNI) ...has been the standard adjuvant treatment for early-stage breast cancer (BC). However, one size does not fit all BC, and the risk of recurrence significantly varies among this patient population. In addition, whether all BC patients presented with one to three positive lymph nodes (pN1) could benefit from IMNI remains controversial. Thus, the optimal adjuvant RNI volume for early-stage BC with T1-2N1 remains undetermined.
The IMNI PRECISION trial is a single institute, open-labeled, non-inferior, randomized controlled trial. A total of 214 clinically "high risk" BC patients which is characterized as having at least two of the five clinically adverse factors (age ≤ 40, three positive LN, T2 stage, grade 3 and Ki-67 index ≥ 14%), but genomic score "low risk" (the genomic score ≤ 44) N1 breast cancers are randomly assigned to omitting IMNI group (experimental group) or with IMNI (control group) with a 1:1 ratio. The primary endpoint of this trial is event-free survival, and secondary endpoints include overall survival and locoregional recurrence-free survival.
The IMNI PRECISION design allows promising clinical-genomic model to stratify the individualized risk of developing recurrence and guides the optimal RNI treatment for early-stage (pT1-2N1) BC patients. We anticipate that our results would provide high-level evidence to tailor IMNI according to individualized recurrence risk of BC.
ClinicalTrials.gov Identifier NCT04517266 . Date of registration: August 18, 2020. Status: Recruiting.
Multi‐modal imaging guided photothermal therapy with single‐walled carbon nanotubes affords effective destruction of primary tumors together with cancer cells in sentinel lymph nodes. This results in ...remarkably prolonged mouse survival compared to mice treated by elimination of only the primary tumor by either surgery or conventional photothermal therapy.
Abstract Context Prostate cancer (PCa) patients with isolated clinical lymph node (LN) relapse, limited to the regional and/or retroperitoneal LNs, may represent a distinct group of patients who have ...a more favorable outcome than men with progression to the bone or to other visceral organs. Some data indirectly denote a beneficial impact of pelvic LN dissection on survival in these patients. Objective To provide an overview of the currently available literature regarding salvage LN dissection (SLND) in PCa patients with clinical relapse limited to LNs after radical prostatectomy (RP). Evidence acquisition A systematic literature search was conducted using the Medline, Embase, and Web of Science databases to identify original articles, review articles, and editorials regarding SLND. Articles published between 2000 and 2012 were reviewed and selected with the consensus of all the authors. Evidence synthesis Contemporary imaging techniques, such as 11C-choline positron emission tomography and diffusion-weighted magnetic resonance imaging, appear to enhance the accuracy in identifying LN relapse in patients with biochemical recurrence (BCR) and after RP. In these individuals, SLND can be considered as a treatment option. The currently available data suggest that SLND can delay clinical progression and postpone hormonal therapy in almost one-third of the patients, although the majority will have BCR. An accurate and attentive preoperative patient selection may help improve these outcomes. The most frequent complication after SLND was lymphorrhea (15.3%), followed by fever (14.5%) and ileus (11.2%). It is noteworthy that all examined cohorts originated from retrospective single-institution series, with limited sample size and short follow-up. Consequently, the current findings cannot be generalized and warrant further investigation in future prospective trials. Conclusions The current data suggest that SLND represents an option in patients with disease relapse limited to the LNs after RP; however, more robust data derived from well-designed clinical trials are needed to validate the role of SLND in this selected patient population. Patient summary Salvage lymph node dissection (SLND) represents a treatment option in for patients with prostate cancer relapse limited to the lymph nodes; however, more robust data derived from well-designed clinical trials are needed to validate the role of SLND in this selected patient population.
Cancer-secreted exosomal miRNAs are emerging mediators of cancer-stromal cross-talk in the tumor environment. Our previous miRNAs array of cervical squamous cell carcinoma (CSCC) clinical specimens ...identified upregulation of miR-221-3p. Here, we show that miR-221-3p is closely correlated with peritumoral lymphangiogenesis and lymph node (LN) metastasis in CSCC. More importantly, miR-221-3p is characteristically enriched in and transferred by CSCC-secreted exosomes into human lymphatic endothelial cells (HLECs) to promote HLECs migration and tube formation in vitro, and facilitate lymphangiogenesis and LN metastasis in vivo according to both gain-of-function and loss-of-function experiments. Furthermore, we identify vasohibin-1 (VASH1) as a novel direct target of miR-221-3p through bioinformatic target prediction and luciferase reporter assay. Re-expression and knockdown of VASH1 could respectively rescue and simulate the effects induced by exosomal miR-221-3p. Importantly, the miR-221-3p-VASH1 axis activates the ERK/AKT pathway in HLECs independent of VEGF-C. Finally, circulating exosomal miR-221-3p levels also have biological function in promoting HLECs sprouting in vitro and are closely associated with tumor miR-221-3p expression, lymphatic VASH1 expression, lymphangiogenesis, and LN metastasis in CSCC patients. In conclusion, CSCC-secreted exosomal miR-221-3p transfers into HLECs to promote lymphangiogenesis and lymphatic metastasis via downregulation of VASH1 and may represent a novel diagnostic biomarker and therapeutic target for metastatic CSCC patients in early stages.
Blood vessels form a closed circulatory system, whereas lymphatic vessels form a one-way conduit for tissue fluid and leukocytes. In most vertebrates, the main function of lymphatic vessels is to ...collect excess protein-rich fluid that has extravasated from blood vessels and transport it back into the blood circulation. Lymphatic vessels have an important immune surveillance function, as they import various antigens and activated antigen-presenting cells into the lymph nodes and export immune effector cells and humoral response factors into the blood circulation. Defects in lymphatic function can lead to lymph accumulation in tissues, dampened immune responses, connective tissue and fat accumulation, and tissue swelling known as lymphedema. This review highlights the most recent developments in lymphatic biology and how the lymphatic system contributes to the pathogenesis of various diseases involving immune and inflammatory responses and its role in disseminating tumor cells.
To determine whether the tumor immune infiltrate, as recently evaluated with the Immunoscore methodology, could be a useful prognostic marker in patients with rectal cancers.
The influence of the ...immune infiltrate on patient's outcome was investigated in patients with or without preoperative chemoradiation therapy (pCRT). The density of total (CD3(+)) and cytotoxic (CD8(+)) T lymphocytes was evaluated by immunohistochemistry and quantified by a dedicated image analysis software in surgical specimens of patients with rectal cancer (n = 111) who did not receive pCRT and in tumor biopsies performed before pCRT from additional 55 patients. The results were correlated with tumor recurrence, patient's survival, and response to pCRT.
The densities of CD3(+) and CD8(+) lymphocytes and the associated Immunoscore (from I0 to I4) were significantly correlated with differences in disease-free and overall survival (HR, 1.81 and 1.72, respectively; all P < 0.005). Cox multivariate analysis supports the advantage of the Immunoscore compared with the tumor-node-metastasis (TNM) staging in predicting recurrence and survival (all P < 0.001). Lymph node ratio added information in a prognostic model (all P < 0.05). In addition, high infiltration of CD3(+) and CD8(+) lymphocytes in tumor biopsies was associated with downstaging of the tumor after pCRT (CD3(+) cells; Fisher exact test P = 0.01).
The Immunoscore could be a useful prognostic marker in patients with rectal cancer treated by primary surgery. The determination of the immune infiltrate in biopsies before treatment could be a valuable information for the prediction of response to pCRT.
Metastasis is a crucial step of malignant progression and is the primary cause of death from endometrial cancer. However, clinicians presently face the challenge that conventional ...surgical‐pathological variables, such as tumour size, depth of myometrial invasion, histological grade, lymphovascular space invasion or radiological imaging are unable to predict with accuracy if the primary tumour has metastasized. In the current retrospective study, we have used primary tumour samples of endometrial cancer patients diagnosed with (n = 16) and without (n = 27) lymph node metastasis to identify potential discriminators. Using peptide matrix assisted laser desorption/ionisation mass spectrometry imaging (MALDI‐MSI), we have identified m/z values which can classify 88% of all tumours correctly. The top discriminative m/z values were identified using a combination of in situ sequencing and LC‐MS/MS from digested tumour samples. Two of the proteins identified, plectin and α‐Actin‐2, were used for validation studies using LC‐MS/MS data independent analysis (DIA) and immunohistochemistry. In summary, MALDI‐MSI has the potential to identify discriminators of metastasis using primary tumour samples.
Background
The SUCCOR cohort was developed to analyse the overall and disease-free survival at 5 years in women with FIGO 2009 stage IB1 cervical cancer. The aim of this study was to compare the use ...of adjuvant therapy in these women, depending on the method used to diagnose lymphatic node metastasis.
Patients and Methods
We used data from the SUCCOR cohort, which collected information from 1049 women with FIGO 2009 stage IB1 cervical cancer who were operated on between January 2013 and December 2014 in Europe. We calculated the adjusted proportion of women who received adjuvant therapy depending on the lymph node diagnosis method and compared disease free and overall survival using Cox proportional-hazards regression models. Inverse probability weighting was used to adjust for baseline potential confounders.
Results
The adjusted proportion of women who received adjuvant therapy was 33.8% in the sentinel node biopsy + lymphadenectomy (SNB+LA) group and 44.7% in the LA group (
p
= 0.02), although the proportion of positive nodal status was similar (
p
= 0.30). That difference was greater in women with negative nodal status and positive Sedlis criteria (difference 31.2%,
p
= 0.01). Here, those who underwent a SNB+LA had an increased risk of relapse hazard ratio (HR) 2.49, 95% confidence interval (CI) 0.98–6.33,
p
= 0.056 and risk of death (HR 3.49, 95% CI 1.04–11.7,
p
= 0.042) compared with those who underwent LA.
Conclusions
Women in this study were less likely to receive adjuvant therapy if their nodal invasion was determined using SNB+LA compared with LA. These results suggest a lack of therapeutic measures available when a negative result is obtained by SNB+LA, which may have an impact on the risk of recurrence and survival.
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