This article provides an overview of radiofrequency ablation (RFA) and microwave ablation (MWA) for treatment of primary liver tumors and hepatic metastasis. Only studies reporting RFA and MWA safety ...and efficacy on liver were retained. We found 40 clinical studies that satisfied the inclusion criteria. RFA has become an established treatment modality because of its efficacy, reproducibility, low complication rates, and availability. MWA has several advantages over RFA, which may make it more attractive to treat hepatic tumors. According to the literature, the overall survival, local recurrence, complication rates, disease‐free survival, and mortality in patients with hepatocellular carcinoma (HCC) treated with RFA vary between 53.2 ± 3.0 months and 66 months, between 59.8% and 63.1%, between 2% and 10.5%, between 22.0 ± 2.6 months and 39 months, and between 0% and 1.2%, respectively. According to the literature, overall survival, local recurrence, complication rates, disease‐free survival, and mortality in patients with HCC treated with MWA (compared with RFA) vary between 22 months for focal lesion >3 cm (vs. 21 months) and 50 months for focal lesion ≤3 cm (vs. 27 months), between 5% (vs. 46.6%) and 17.8% (vs. 18.2%), between 2.2% (vs. 0%) and 61.5% (vs. 45.4%), between 14 months (vs. 10.5 months) and 22 months (vs. no data reported), and between 0% (vs. 0%) and 15% (vs. 36%), respectively. According to the literature, the overall survival, local recurrence, complication rates, and mortality in liver metastases patients treated with RFA (vs. MWA) are not statistically different for both the survival times from primary tumor diagnosis and survival times from ablation, between 10% (vs. 6%) and 35.7% (vs. 39.6), between 1.1% (vs. 3.1%) and 24% (vs. 27%), and between 0% (vs. 0%) and 2% (vs. 0.3%). MWA should be considered the technique of choice in selected patients, when the tumor is ≥3 cm in diameter or is close to large vessels, independent of its size.
Implications for Practice
Although technical features of the radiofrequency ablation (RFA) and microwave ablation (MWA) are similar, the differences arise from the physical phenomenon used to generate heat. RFA has become an established treatment modality because of its efficacy, reproducibility, low complication rates, and availability. MWA has several advantages over RFA, which may make it more attractive than RFA to treat hepatic tumors. The benefits of MWA are an improved convection profile, higher constant intratumoral temperatures, faster ablation times, and the ability to use multiple probes to treat multiple lesions simultaneously. MWA should be considered the technique of choice when the tumor is ≥3 cm in diameter or is close to large vessels, independent of its size.
A review of the literature on the safety and efficacy of radiofrequency ablation and microwave ablation on the liver was conducted. This article summarizes the results, focusing on treatment of primary liver tumors and hepatic metastasis.
Invariant natural killer T cell (iNKT) cells produce large amounts of cytokines in response to α-Galactosylceramide (α-GalCer) stimulation. An analog containing two phenyl rings on the acyl chain, ...C34, was previously found to be more Th1-biased than α-GalCer and triggered greater anticancer activities against breast cancer, melanoma and lung cancer in mice. Since liver is enriched in iNKT cells, we investigated anticancer efficacy of C34 on neuroblastoma with hepatic metastasis. C34 induced Th1-biased cytokine secretions in the liver, significantly suppressed neuroblastoma growth/metastasis and prolonged mouse survival. The anti-tumor efficacy might be attributed to greater expansions of hepatic NKT, NK, CD4+ T, and CD8+ T cells as well as reduction of the number of SSCloGr1intCD11b+ subset of myeloid-derived suppressor cells (MDSCs) in the liver of tumor-bearing mice, as compared to DMSO control group. C34 also upregulated expression of CD1d and CD11c, especially in the SSCloGr1intCD11b+ subset of MDSCs, which might be killed by C34-activated NKT cells, attributing to their reduced number. In addition, C34 also induced expansion of CD4+ T, CD8+ T, and NK cells, which might eliminate neuroblastoma cells. These immune-modulating effects of C34 might act in concert in the local milieu of liver to suppress the tumor growth. Further analysis of database of neuroblastoma revealed that patients with high CD11c expression in the monocytic MDSCs in the tumor had longer survival, suggesting the potential clinical application of C34 for treatment of neuroblastoma.
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•Phase I trial of GD2 CAR-NKT cell therapy shows encouraging results in neuroblastoma.•Clinical translation of GD2 CAR-NKT is challenging due to its rarity and difficulty in expansion.•C34, which activates NKT cells without inducing anergy, shows therapeutic potential for neuroblastoma.•C34 elicited Th1 cytokines and activated/expanded NKT cells while reduced MDSCs and Treg cells in the liver.•C34-activated NKT may target CD1d (-) neuroblastoma cells indirectly via activation of NK cells.
Cancer cells rewire metabolism to sculpt the immune tumor microenvironment (TME) and propel tumor advancement, which intricately tied to post-translational modifications. Histone lactylation has ...emerged as a novel player in modulating protein functions, whereas little is known about its pathological role in pancreatic ductal adenocarcinoma (PDAC) progression. Employing a multi-omics approach encompassing bulk and single-cell RNA sequencing, metabolomics, ATAC-seq, and CUT&Tag methodologies, we unveiled the potential of histone lactylation in prognostic prediction, patient stratification and TME characterization. Notably, "LDHA-H4K12la-immuno-genes" axis has introduced a novel node into the regulatory framework of "metabolism-epigenetics-immunity," shedding new light on the landscape of PDAC progression. Furthermore, the heightened interplay between cancer cells and immune counterparts via Nectin-2 in liver metastasis with elevated HLS unraveled a positive feedback loop in driving immune evasion. Simultaneously, immune cells exhibited altered HLS and autonomous functionality across the metastatic cascade. Consequently, the exploration of innovative combination strategies targeting the metabolism-epigenetics-immunity axis holds promise in curbing distant metastasis and improving survival prospects for individuals grappling with challenges of PDAC.
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•Histone lactylation signature potentially indicates a poor prognosis and delineates the suppressive tumor immune microenvironment in pancreatic ductal adenocarcinoma (PDAC).•The axis involving LDHA-H4K12la-immuno-genes operates in immune evasion to promote the progression of PDAC.•Increased interaction between cancer cells and immune counterparts mediated by Nectin-2 in liver metastasis of elevated histone lactylation signature, reveals a positive feedback loop that drives immune evasion.
Background: Liver metastasis of colon cancer is strongly affected by the tumor microenvironment (TME), with interactions between tumor cells and cancer-associated fibroblasts (CAFs) in particular. ...TGF-β is well known for its ability to mediate the CAF phenotype, and CXCR4 expression is closely correlated to poor prognosis in CRC. The relationship between these two signaling pathways remains to be delineated in liver metastasis of colon cancer.
Methods: Immunohistochemistry was employed to investigate CXCR4 expression in 45 human specimens of primary colorectal cancer (CRC) and liver metastasis. The functions of SDF-1 released by hepatic stellate cells (HSCs) on CXCR4 and TGF-β1 in CRC cells were investigated in vitro. The effects of CRC on HSCs differentiation into CAFs were confirmed using co-culture technology and expression analysis of CAFs markers by qPCR, western blot and immunofluorescence. The involvement of CXCR4 and TGF-β1 was verified with addition of CXCR4 inhibitor AMD3100 and TGF-β1 inhibitor cyclophosphamide (Cy) both in vitro and in vivo.
Results: There were more CXCR4-positive cells at the liver metastatic tissues compared to the primary sites. CRC cells activated and transformed HSCs to CAFs after co-cultivating with HSCs. Activated HSCs stimulated TGF-β1 secretion from CRC cells after co-culture with CRC cells in vitro. Moreover, the expression of CAFs markers was increasing in the activated HSCs. In a mouse hepatic metastasis model, treated with AMD3100 or Cy blocked the metastatic potential of HCT116 cells and the hepatic CAFs differentiation.
Conclusions: These results indicated that CXCR4/TGF-β1 axis plays an important role in CRC liver metastasis through mediating HSCs differentiation into CAFs, providing preclinical evidences that blockade of the axis might be beneficial for anti-metastasis therapy in CRC.
•This study is the first to explore the impact of organ-specific tumor response to enfortumab vedotin in patients with metastatic urothelial carcinoma.•The most prominent organ-specific response rate ...was found in liver metastasis, and the least in bone metastasis.•Tumor burden reduced by 50% or more in lymph node, lung, and liver metastases.•No prognostic differences were found with respect to the organ-specific overall survival.
To evaluate the organ-specific therapeutic effect of enfortumab vedotin (EV) after chemotherapy and immunotherapy failed for advanced urothelial carcinoma.
At 6 institutions between December 2021 and July 2023, we retrospectively analyzed patients with metastatic upper and lower urinary tract cancer who received EV monotherapy after platinum-based chemotherapy and immune checkpoint blockade therapy. Objective response rate (ORR) and organ-specific response rate (OSRR) were evaluated according to the Response Evaluation Criteria in Solid Tumors, version 1.1.
This study analyzed 58 patients with 210 tumor lesions, of which 24% were females and 48% had upper urinary tract cancer. The ORR and disease control rate were 53.5% and 74.1%. Moreover, we found 15 target lesions in the primary site, 7 in local recurrence, 93 in the lymph nodes, 46 in the lung, 29 in the liver, and 20 in the bone, with OSRRs of 40%, 71.4%, 61.1%, 70.6%, 90.9%, and 18.2%, respectively. Over time from baseline, the reduction rate (median) in tumor burden was 50% or more in the lymph node, lung, and liver metastases.
The organ-specific tumor response to EV in patients with metastatic urothelial carcinoma was almost favorable. The antitumor activity of EV monotherapy may be less in bone metastasis than in other organ sites. Conversely, EV showed remarkably high efficacy against liver metastasis.
Advanced urothelial carcinoma with metastasis is clinically aggressive. We evaluated the organ-specific response to enfortumab vedotin treatment after platinum-based chemotherapy and immune checkpoint blockade therapy failed in patients with metastatic bladder and upper urinary tract cancer. A promising antitumor activity was observed regardless of the organ involved.
The occurrence of liver metastasis significantly affects the prognosis of colorectal cancer (CRC). Existing research indicates that primary tumor location, vascular invasion, lymph node metastasis, ...and abnormal preoperative tumor markers are risk factors for CRC liver metastasis. Positive expression of programmed cell death ligand 1 (PD-L1) may serve as a favorable prognostic marker for nasopharyngeal and gastric cancers, in which combined positive score (CPS) quantifies the level of PD-L1 expression. This study aimed to explore CPS as a potential risk factor for CRC liver metastasis and integrate other independent risk factors to establish a novel predictive model for CRC liver metastasis.
A retrospective analysis was conducted on 437 patients with CRC pathologically diagnosed at The Second Xiangya Hospital of Central South University from January 1, 2019, to December 31, 2021. Data were collected, including CPS, age, gender (male and female), primary tumor location, Ki-67 expression, pathologic differentiation, neural invasion, vascular invasion, lymph node metastasis, and preoperative tumor markers. The optimal cutoff point for the continuous variable CPS was determined using the Youden index, and all CPSs were dichotomized into high- and low-risk groups based on this threshold (scores below the threshold were considered high risk, and score above the threshold were considered low risk). Univariate logistic regression analysis was employed to identify risk factors for CRC liver metastasis, followed by multivariate logistic regression analysis to integrate the selected risk factors. The predictive model was validated through the construction of receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). A nomogram was constructed for visualization.
The determined cutoff point for PD-L1 CPS was 4.5, with scores below this threshold indicating a high risk of CRC liver metastasis. In addition, primary tumor origin other than the rectum, presence of pericolonic lymph node metastasis, and abnormal levels of tumor markers carcinoembryonic antigen and cancer antigen 19-9 were identified as independent risk factors for CRC liver metastasis. The constructed clinical prediction model demonstrated good predictive ability and accuracy, with an area under the ROC curve of 0.871 (95% CI, 0.838-0.904).
The exploration and validation of CPS as a novel predictor of CRC liver metastasis were performed. Based on these findings, a new clinical prediction model for CRC liver metastasis was developed by integrating other independent risk factors. The DCA, clinical impact curve, and nomogram graph constructed on the basis of this model have significant clinical implications and guide clinical practice.
Mounting evidence has demonstrated the vital importance of tumor-associated macrophages (TAMs) and exosomes in the formation of the premetastatic niche. However, the molecular mechanisms by which ...tumor-derived exosomal miRNAs interact with TAMs underlying premetastatic niche formation and colorectal cancer liver metastasis (CRLM) remain largely unknown.
Transmission electron microscopy and differential ultracentrifugation were used to verify the existence of exosomes. In vivo and in vitro assays were used to identify roles of exosomal miR-934. RNA pull-down assay, dual-luciferase reporter assay, etc. were applied to clarify the mechanism of exosomal miR-934 regulated the crosstalk between CRC cells and M2 macrophages.
In the present study, we first demonstrated the aberrant overexpression of miR-934 in colorectal cancer (CRC), especially in CRLM, and its correlation with the poor prognosis of CRC patients. Then, we verified that CRC cell-derived exosomal miR-934 induced M2 macrophage polarization by downregulating PTEN expression and activating the PI3K/AKT signaling pathway. Moreover, we revealed that hnRNPA2B1 mediated miR-934 packaging into exosomes of CRC cells and then transferred exosomal miR-934 into macrophages. Interestingly, polarized M2 macrophages could induce premetastatic niche formation and promote CRLM by secreting CXCL13, which activated a CXCL13/CXCR5/NFκB/p65/miR-934 positive feedback loop in CRC cells.
These findings indicate that tumor-derived exosomal miR-934 can promote CRLM by regulating the crosstalk between CRC cells and TAMs. These findings reveal a tumor and TAM interaction in the metastatic microenvironment mediated by tumor-derived exosomes that affects CRLM. The present study also provides a theoretical basis for secondary liver cancer.
The tumor microenvironment (TME) is connected to immunotherapy responses, but it remains unclear how cancer cells and host tissues differentially influence the immune composition within TME. Here, we ...performed single-cell analyses for autologous samples from liver metastasized colorectal cancer to disentangle factors shaping TME. By aligning CD45+ cells across different tissues, we classified exhausted CD8+ T cells (Texs) and activated regulatory T cells as M-type, whose phenotypes were associated with the malignancy, while natural killer and mucosal-associated invariant T cells were defined as N-type, whose phenotypes were associated with the niche. T cell receptor sharing between Texs in primary and metastatic tumors implicated the presence of common peripheral non-exhausted precursors. For myeloid cells, a subset of dendritic cells (DC3s) and SPP1+ macrophages were M-type, and the latter were predominant in liver metastasis, indicating its pro-metastasis role. Our analyses bridge immune phenotypes of primary and metastatic tumors, thereby helping to understand the tumor-specific contexture and identify the pro-metastasis components.
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•Immune cell phenotypic linkage with colorectal cancer and liver metastasis depicted•Malignancy-associated exhausted and regulatory T cells show diverse TCR dependency•SPP1+ TAMs are malignancy associated and are linked to liver metastasis•DCs are mainly associated with host organ except a malignancy-associated DC3 subset
Liu et al. reveal the roles of malignancy and host-organ contexture in shaping immune infiltrates within a tumor microenvironment based on single-cell phenotypic alignment of colorectal cancer and the autologous liver metastasis
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