Cancer dissemination to lymph nodes (LN) is associated with a worse prognosis, increased incidence of distant metastases and reduced response to therapy. The LN microenvironment puts selective pressure on cancer cells, creating cells that can survive in LN as well as providing survival advantages for distant metastatic spread. Additionally, the presence of cancer cells leads to an immunosuppressive LN microenvironment, favoring the evasion of anti-cancer immune surveillance. However, recent studies have also characterized previously unrecognized roles for tumor-draining lymph nodes (TDLNs) in cancer immunotherapy response, including acting as a reservoir for pre-exhausted CD8+ T cells and stem-like CD8+ T cells. In this review, we will discuss the spread of cancer cells through the lymphatic system, the roles of TDLNs in metastasis and anti-cancer immune responses, and the therapeutic opportunities and challenges in targeting LN metastasis.

Thyroid cancer with metastatic disease to the pelvis is extremely rare. The patient in our case, an 86-year-old male, presented after total thyroidectomy for follicular thyroid cancer (FTC) with symptoms of recurrent urinary tract infections and retentions, surprisingly leading to the discovery of a large sacral mass on the CT abdomen and pelvis. The biopsy showed metastatic carcinoma with morphology and immunohistochemistry to be consistent with FTC. In our case, due to symptomatology, prostate cancer was initially considered high in the differential for primary source rather than thyroid cancer. The mass was considered too large for surgery, and he was referred to a radiation oncologist for radiation therapy for the sacral mass.

Nasopharyngeal carcinoma (NPC) is prevalent in Asia and exhibits highly metastatic characteristics, leading to uncontrolled disease progression. Isoliquiritigenin (ISL) have attracted attention due to their diverse biological and pharmacological properties, including anticancer activities. However, the impact of ISL on the invasive and migratory ability of NPC remains poorly understood. Hence, this study aimed to investigate the in vitro anti-metastatic effects of ISL on NPC cells and elucidate the underlying signalling pathways. Human NPC cell NPC-39 and NPC-BM were utilized as cell models. Migratory and invasive capabilities were evaluated through wound healing and invasion assays, respectively. Gelatin zymography was employed to demonstrate matrix metalloproteinase-2 (MMP-2) activity, while western blotting was conducted to analyse protein expression levels and explore signalling cascades. Overexpression of signal transducer and activator of transcription 3 (STAT3) was carried out by transduction of STAT3-expressing vector. Our findings revealed that ISL effectively suppressed the migration and invasion of NPC cells. Gelatin zymography and Western blotting assays demonstrated that ISL treatment led to a reduction in MMP-2 enzyme activity and protein expression. Investigation of signalling cascades revealed that ISL treatment resulted in the inhibition of STAT3 phosphorylation. Moreover, overexpression of STAT3 restored the migratory ability of NPC cells in the presence of ISL. Collectively, these findings indicate that ISL inhibits the migration and invasion of NPC cells associating with MMP-2 downregulation through suppressing STAT3 activation. This suggests that ISL has an anti-metastatic effect on NPC cells and has potential therapeutic benefit for NPC treatment.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, often diagnosed at the advanced stage (metastatic). Treatment options for metastatic NSCLC include radiotherapy, chemotherapy, target drug therapy, and immunotherapy. Immunotherapy (utilization of checkpoint inhibitors) boosts the immune system to recognize and destroy cancer cells. However, it is often associated with immune-related complications such as pneumonitis. This review aims to determine the incidence of pneumonitis in metastatic NSCLC patients treated with different immunotherapy drugs. PubMed, Cochrane Library, and Embase databases were scoured for randomized controlled trials (RCTs) until October 2023. Published RCTs with similar research objectives were included, while non-English articles, reviews, case reports, ongoing trials, non-randomized studies, conference abstracts, and studies on small cell lung cancer (SCLC) were excluded. The Cochrane risk-of-bias tool for randomized trials (RoB 2) was used to assess the risk of bias among the included studies. The statistical analyses were performed with the Comprehensive Meta-Analysis software. The subgroup analysis of the 16 included RCTs showed that metastatic NSCLC patients treated with nivolumab and pembrolizumab had a higher incidence of any grade pneumonitis than those treated with atezolizumab (4.5% and 5.1% vs. 1.6%, respectively). Similarly, the incidence of grade ≥3 pneumonitis was higher among patients receiving nivolumab (1.3%) and pembrolizumab (2.4%) than those receiving atezolizumab (0.7%). Furthermore, the subgroup analysis showed that patients with naive-treated NSCLC on immunotherapy had a higher incidence of any grade pneumonitis than those with previously treated NSCLC (6.5% vs. 3.9%). Treatment-naive patients recorded higher grade ≥3 pneumonitis incidences than those previously treated (3.1% vs. 1.3%). Programmed death 1 (PD-1) inhibitors (i.e., pembrolizumab and nivolumab) have higher incidences of pneumonitis than programmed death-ligand 1 inhibitors (atezolizumab).

Tumor-derived exosomes bind to organ resident cells, activating S100 molecules during the remodeling of the local immune microenvironment. However, little is known regarding how organ resident cell S100A10 mediates cancer metastatic progression. Here, we provided evidence that S100A10 plays an important role in regulating the lung immune microenvironment and cancer metastasis. S100A10-deficient mice reduced cancer metastasis in the lung. Furthermore, the activation of S100A10 within lung fibroblasts via tumor-derived exosomes increased the expression of CXCL1 and CXCL8 chemokines, accompanied by the myeloid-derived suppressor cells (MDSCs) recruitment. S100A10 inhibitors such as 1-Substituted-4-Aroyl-3-hydroxy-5-Phenyl-1 H-5-pyrrol-2(5 H)-ones inhibit lung metastasis in vivo. Our findings highlight the crucial role of S100A10 in driving MDSC recruitment in order to remodel the lung immune microenvironment and provide potential therapeutic targets to block cancer metastasis to the lung.

Studies have identified genes and molecular pathways regulating cancer metastasis. However, it remains largely unknown whether metastatic potentials of cancer cells from different lineage types are driven by the same or different gene networks. Here, we aim to address this question through integrative analyses of 493 human cancer cells\' transcriptomic profiles and their metastatic potentials in vivo. Using an unsupervised approach and considering both gene coexpression and protein-protein interaction networks, we identify different gene networks associated with various biological pathways (i.e. inflammation, cell cycle, and RNA translation), the expression of which are correlated with metastatic potentials across subsets of lineage types. By developing a regularized random forest regression model, we show that the combination of the gene module features expressed in the native cancer cells can predict their metastatic potentials with an overall Pearson correlation coefficient of 0.90. By analyzing transcriptomic profile data from cancer patients, we show that these networks are conserved in vivo and contribute to cancer aggressiveness. The intrinsic expression levels of these networks are correlated with drug sensitivity. Altogether, our study provides novel comparative insights into cancer cells\' intrinsic gene networks mediating metastatic potentials across different lineage types, and our results can potentially be useful for designing personalized treatments for metastatic cancers.

Whether cancer cells metastasize from the primary site to the distant sites via the lymphatic vessels or the blood vessels directly into the circulation is still under intense study. In this review article, we follow the journey of cancer cells metastasizing to the sentinel lymph nodes and beyond to the distant sites. We emphasize cancer heterogeneity and microenvironment as major determinants of cancer metastasis. Multiple molecules have been found to be associated with the complicated process of metastasis. Based on the large sentinel lymph node data, it is reasonable to conclude that cancer cells may metastasize through the blood vessels in some cases but in most cases, they use the sentinel lymph nodes as the major gateway to enter the circulation to distant sites.

We present the case of a 42-year-old female with a history of human epidermal growth factor 2 (HER2) receptor-positive breast cancer status post bilateral mastectomy with metastasis to the spine and to the brain, who underwent transesophageal echocardiography (TEE) after outpatient transthoracic echocardiography (TTE) was suggestive of right atrial thrombus in transit. TEE revealed an atrial mass with a pedunculated stalk attached to the inferior right atrium near the inferior vena cava with a necrotic center. These findings were suggestive of an endocardial metastatic mass secondary to her primary breast cancer. The pericardium is the most common site of cardiac metastasis; meanwhile, endocardial involvement is infrequent, occurring in less than 5% of all cardiac metastases. Right atrial masses may cause evidence of right heart failure and thromboembolism of the pulmonary arteries. Treatment focuses on targeted chemotherapy, radiation therapy, and interventions as indicated. In this case, following the diagnosis of a right atrial mass, the patient was discharged the same day to begin outpatient chemotherapy.

BACKGROUND: Rectal mucinous adenocarcinoma (MAC) is a rare pathological type of rectal cancer with unique pathological features and a poor prognosis. It is difficult to diagnose and treat early because of the lack of specific manifestations in some aspects of the disease. The common metastatic organs of rectal cancer are the liver and lung; however, rectal carcinoma with metastasis to subcutaneous soft tissue is a rare finding.
METHODS: In this report, the clinical data, diagnosis and treatment process, and postoperative pathological features of a patient with left waist subcutaneous soft tissue masses were retrospectively analyzed. The patient underwent surgical treatment after admission and recovered well after surgery. The final pathological diagnosis was rectal MAC with left waist subcutaneous soft tissue metastasis.
CONCLUSIONS: Subcutaneous soft tissue metastasis of rectal MAC is rare, and it can suggest that the tumor is disseminated, and it can appear even earlier than the primary malignant tumor, which is occult and leads to a missed diagnosis and misdiagnosis clinically. When a subcutaneous soft tissue mass of unknown origin appears in a patient with rectal cancer, a malignant tumor should be considered.

BACKGROUND: Circulating tumor cells (CTCs) are considered as a useful biomarker for early cancer diagnosis, which play a crucial role in metastatic process. Unfortunately, the tumor heterogeneity and extremely rare occurrence rate of CTCs among billions of interfering leukocytes seriously hamper the sensitivity and purity of CTCs isolation.
METHODS: To address these, we firstly used microfluidic chips to detect the broad-spectrum of triple target combination biomarkers in CTCs of 10 types of cancer patients, including EpCAM, EGFR and Her2. Then, we constructed hybrid engineered cell membrane-camouflaged magnetic nanoparticles (HE-CM-MNs) for efficient capture of heterogeneous CTCs with high-purity, which was enabled by inheriting the recognition ability of HE-CM for various CTCs and reducing homologous cell interaction with leukocytes. Compared with single E-CM-MNs, HE-CM-MNs showed a significant improvement in the capture efficiency for a cell mixture, with an efficiency of 90%. And the capture efficiency of HE-CM-MNs toward 12 subpopulations of tumor cells was ranged from 70 to 85%. Furthermore, by using HE-CM-MNs, we successfully isolated heterogeneous CTCs with high purity from clinical blood samples. Finally, the captured CTCs by HE-CM-MNs could be used for gene mutation analysis.
CONCLUSIONS: This study demonstrated the promising potential of HE-CM-MNs for heterogeneous CTCs detection and downstream analysis.