The introduction of new target therapies and immunotherapy combinations has dramatically improved the prognosis of cancer patients. Surgery and radiotherapy currently represent the cornerstones of loco-regional management, both for palliative and curative purposes. It is no coincidence, therefore, that in recent years the frequency of complications once considered rare has increased.

Here we present the case of a patient affected by metastatic bladder cancer whose treatments (surgery, radiotherapy, and targeted therapy) favored a rapid and acute onset of Fournier syndrome. The fulminant course prevented the establishment of a potentially effective treatment.

Fournier gangrene is an acute perineal necrosis caused by anaerobic bacteria. Management is complex and requires a quick multidisciplinary approach, even though, among cancer patients, mortality is very high.

Transmembrane proteins (TMEMs) constitute a large family of proteins that span biological membranes and are distributed across various cellular organelles, playing key roles in maintaining cellular homeostasis. Increasing evidence has revealed that dysregulation of TMEMs is closely associated with cancer development and progression. Therefore, a deeper understanding of the relationship between TMEMs and cancer is essential. Different TMEMs can function either as oncogenes or tumour suppressors, depending on the context. In this review, we explore the involvement of TMEMs in cancer, categorizing them into three groups based on their roles: oncogenic, tumour-suppressive or dual-function (both oncogenic and tumour-suppressive). We summarize the roles of various TMEMs in different cancer types, highlighting both well-characterized proteins and those identified through database screening, even if their exact molecular mechanisms remain unclear. Where possible, we include known signalling pathways associated with these TMEMs. This review highlights the critical roles of the TMEM protein family and encourages further research into their mechanisms, prognostic value and potential as targets for cancer therapy.

Skin cancers, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), cutaneous melanoma (CM) and acral melanoma (AM), exhibit profound heterogeneity in clinical behaviour and therapeutic response. However, how tumour-immune ecosystems are remodelled across skin cancer types and disease stages, and how these changes influence immune escape and treatment resistance, remain poorly understood.

Here, we integrate single-cell transcriptomics data from 102 skin cancer samples (including adjacent normal skin, early-stage and advanced-stage tumours), with bulk RNA-seq prognosis cohorts, immunofluorescence staining and in vitro assays to define clinically relevant immune remodelling patterns.

Our analyses identify a malignant NARS2⁺NDUFC2⁺ melanoma cell subpopulation, characterised by reduced MHC-I expression, enriched in advanced-stage tumours and associated with worse survival and immunotherapy response. CRISPR screening further showed that NARS2 and NDUFC2 are necessary for the proliferation of melanoma cells, highlighting these genes as potential therapeutic targets. Tumour-associated macrophages (TAMs) originate from both FCN1⁺ monocytes and FOLR2⁺ tissue-resident macrophages, displaying two polarisation states with distinct prognostic associations. Specifically, pro-inflammatory CXCL9⁺CXCL10⁺ TAMs are enriched in SCC, while tissue-remodelling SPP1⁺ TAMs are predominant in melanoma. Immunofluorescence staining confirmed that SPP1⁺ macrophage accumulation correlates with advanced stage, metastasis and poor prognosis in the melanoma cohort. Immune ecotype analysis reveals a transition from 'T-cell-dominant' ecotypes to 'desert' ecotypes as disease advances in BCC, CM and AM. Cell‒cell communication analysis shows that 'T-cell-dominant' ecotypes have higher MHC-I signalling pathways in tumour cells, whereas 'Desert' ecotypes have higher SPP1⁺ macrophage signalling, underlining the role of SPP1 on immune remodelling. Functional assays confirm that melanoma cells could drive M2 polarisation and SPP1 upregulation in macrophages. Knocking down or overexpressing SPP1 correspondingly alters M2 gene expression in macrophages.

This study establishes a pan-skin cancer immune remodelling framework, providing a foundation for biomarker discovery and the development of new immunotherapy strategies.

Squamous papilloma (SP) of the external ear is a rare benign neoplasm, with limited research on its associated human papillomavirus (HPV) infections and pathologic features. This study aims to provide a comprehensive analysis of the largest case series of external ear SP from Southwest China. We retrospectively collected 88 cases diagnosed with SP in the external ear canal, of which 85 (97%) were located in the external auditory canal and 3 (3%) on the auricle. We investigated the clinical, pathological, and HPV-typing characteristics using Polymerase chain reaction (PCR) and reverse dot blot (RDB) hybridization. Our series included 74 males and 14 females, with a median age of 62.5 years (range: 5-91 years). The predominant HPV type was HPV-6 (59/62, 95.2%), followed by high-risk types HPV-16 (4/62, 6.5%), HPV-52 (2/62, 3.2%), and HPV-58 (1/62, 1.6%). Histologically, all cases demonstrated typical features of SP, including koilocytes, hyperkeratosis, and basal/parabasal hyperplasia. Additionally, co-infection with multiple HPV types was observed in four cases. Notably, high-risk HPV types were detected in seven cases, all of which were completely excised with no recurrence during follow-up. This study suggests regional variations in HPV-subtype distribution and highlights potential environmental factors contributing to the prevalence of SP in Southwest China.

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, characterized by poor prognosis and limited therapeutic efficacy. Ginkgo biloba extract (GBE) has demonstrated antitumor potential, yet its precise molecular mechanisms in HCC are not fully understood.

This study aimed to elucidate how GBE suppresses HCC progression and to explore its underlying molecular mechanisms.

A subcutaneous HCC mouse model was established to evaluate the antitumor effects of GBE in vivo. Network pharmacology, molecular docking, and in vitro assays were integrated to identify and validate the core molecular targets of GBE.

GBE treatment significantly inhibited tumor growth and reduced myeloid-derived suppressor cells (MDSCs) recruitment within the tumor microenvironment. Network pharmacology identified proto-oncogene tyrosine-protein kinase (SRC) as a key target of GBE. Molecular docking revealed strong spontaneous binding affinity between active GBE components and SRC. In vitro experiments confirmed that GBE markedly downregulated SRC expression and CXCL1 secretion in HCC cells, whereas SRC overexpression reversed these effects. Clinical data further showed that SRC was upregulated in HCC tissues and correlated with poor prognosis and elevated MDSCs infiltration.

GBE suppresses HCC progression by downregulating SRC expression, which consequently reduces CXCL1 secretion and limits MDSCs recruitment within the tumor. These findings highlight GBE as a promising adjuvant immunotherapeutic strategy for HCC.

Colorectal cancer (CRC) ranks among the most prevalent malignancies, with increasing incidence and mortality rates presenting a substantial public health challenge. While insulin growth factor like family member 1 (IGFL1) has been implicated in the regulation of various diseases, its functional role in colorectal cancer remains poorly characterised. This study therefore aims to elucidate the involvement of IGFL1 in CRC through an integrated approach combining bioinformatics analysis and experimental validation.

The expression of IGFL1 in CRC and its association with clinicopathological features, diagnostic relevance, and patient prognosis were evaluated using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Immunohistochemistry was performed to validate IGFL1 protein expression in CRC tissue samples. Immune cell infiltration levels and immune microenvironment scores related to IGFL1 expression were analysed using multiple computational algorithms, including CIBERSORT, ssGSEA, ESTIMATE, EPIC, MCP-counter, quanTIseq, TIMER, xCell, and CIBERSOR. Furthermore, IGFL1 expression patterns across distinct cellular subpopulations were examined using single-cell RNA sequencing datasets from the Tumor Immune Single-cell Hub (TISCH) database. The TIDE algorithm was applied to assess the potential clinical efficacy of immunotherapy in groups with high versus low IGFL1 expression, in addition to investigating correlations between IGFL1 expression and immune checkpoint markers. Genetic alterations of IGFL1 were analysed via cBioPortal, while the TIMER2.0 database was used to explore relationships between IGFL1 expression and key gene mutations in CRC. The CTRP and GDSC databases were employed to investigate associations between IGFL1 expression and sensitivity to conventional chemotherapy drugs. Finally, phenotypic validation and mechanistic studies were conducted using the CRC cell lines SW620 and HCT116.

Our study demonstrates that IGFL1 expression is significantly up-regulated in CRC and possesses considerable diagnostic value. Elevated IGFL1 levels were consistently observed in clinical specimens, where high expression correlated with adverse clinicopathological features, poorer prognosis, and mutations in key oncogenes. Within the tumour microenvironment, IGFL1 appears to play a critical role in modulating the infiltration of diverse immune cell populations. Furthermore, IGFL1 expression influences both immunotherapy responsiveness and chemotherapy sensitivity in CRC patients. Genetic knockdown of IGFL1 markedly attenuated the malignant phenotype of CRC cells. RNA-sequencing analysis revealed that IGFL1 is closely linked to cholesterol metabolism, autophagy pathways, and ATP hydrolysis activity. Functionally, inhibition of IGFL1 enhanced lipophagy in CRC cells. Collectively, these findings indicate that IGFL1 promotes CRC pathogenesis and progression through the suppression of lipophagy.

IGFL1 exhibits oncogenic properties in colorectal cancer and may represent a potential therapeutic target.

Chimeric antigen receptor T cell (CAR-T) therapy faces multiple challenges in solid tumors, especially the heterogeneity of tumor antigens. Glypican-3 (GPC3) and trophoblast cell-surface antigen 2 (TROP2) are highly expressed antigens in lung squamous cell carcinoma (LUSC) for development of dual-targeted therapy. The absence of GPC3 in any normal tissues of adults makes it an ideal target for CAR-T therapy. However, TROP2 is expressed in the epithelial cells of various normal tissues and thus is not acceptable for direct design of CAR-T therapy due to the high risk of "on-target off-tumor" effects. Here we developed a dual-targeted LUSC therapy featuring a GPC3-targeted CAR-T cell secreting TROP2-directed bispecific T cell engagers (GPC3 CAR-T. TROP2 BiTE), and verified the antitumor activity in vitro and in vivo, respectively.

Immunohistochemistry (IHC) was used to confirm the expression of GPC3 and TROP2 in LUSC and normal tissues. CAR-T cells were produced through lentiviral transduction of CAR genes. Real-time cytotoxicity assay (RTCA) was used to assess the cytotoxic effect of CAR-T cells on LUSC cells. Flow cytometry was utilized to examine the CAR-T cell phenotype, exhaustion and activation. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the release of cytokines. To evaluate the activity of CAR-T cells in vivo, tumor-bearing immunodeficient mice were given a single intravenous injection of CAR-T cells, and the tumor burden and CAR-T cell expansion were regularly monitored.

GPC3 was overexpressed in 70% of LUSC tissues, while negatively expressed in all normal tissues. Positive expression of TROP2 was observed in all LUSC tissues and also in many normal tissues. Compared with GPC3 CAR-T and TROP2 CAR-T, GPC3 CAR-T. TROP2 BiTE exhibited cytotoxicity to both GPC3⁺ and TROP2⁺ LUSC cells, and thereby showed faster killing and durable antitumor effect against LUSC cells with heterogenous expression of GPC3 and TROP2. In tumor-bearing mice, GPC3 CAR-T. TROP2 BiTE showed strong ability to eliminate tumors.

This study demonstrated that GPC3 CAR-T. TROP2 BiTE was a potent therapy for LUSC and provided a strategy for overcoming the antigen heterogeneity in solid tumors.

Tumefactive demyelination is a rare phenotypic subtype of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) and poses significant diagnostic challenges due to substantial clinical and radiological overlap with intracranial neoplasms and other demyelinating conditions. This mimicry frequently leads to misdiagnosis and subsequent inappropriate therapeutic interventions and delay in treatment, thereby increasing the risk of adverse clinical outcomes. We present the case of a 31-year-old male with a prior history of MOG-associated optic neuritis (ON) who developed acute-onset dizziness and gait instability evolving over five days. Brain magnetic resonance imaging (MRI) demonstrated an atypical mass-like lesion in the left cerebellar hemisphere with extension to the middle cerebellar peduncle. Serum testing showed MOG-IgG positivity at 1:100 titer (live cell-based assay) with negative AQP4-IgG. Following timely pulse corticosteroid therapy, the patient showed marked symptomatic improvement and received sequential maintenance of oral corticosteroid for six months. A follow-up MRI revealed complete resolution of abnormalities, and no recurrence was observed during the 21-month follow-up period. This case highlights the critical importance of including rare tumefactive MOGAD in the differential diagnosis of mass-like lesions, thereby avoiding the potential morbidity associated with misdiagnosis and delayed treatment. It also underscores the role of maintenance therapy in reducing relapses and preventing disability accumulation.

Macrophages are pivotal regulators of immunity, with intercellular communication being a central mechanism of their function. Among these communications, chemokines act as critical messengers in macrophage-T cell crosstalk. This review systematically elucidates the notable roles of macrophage-derived chemokines in modulating T cell homeostasis, particularly concentrating on their influence on both CD4⁺ and CD8⁺ T cell differentiation, proliferation, exhaustion, secretory activity, metabolic reprogramming (involving glycolysis and OXPHOS), chemotaxis, and memory formation. In the tumor microenvironment (TME), the dualistic nature of chemokines was highlighted: tumor-associated macrophages (TAMs) could secrete immunosuppressive factors, such as CCL22 and CCL5, recruiting inhibitory cells and inducing CD8⁺ T cell exhaustion. In contrast, M1-like macrophages could produce CXCL9 and CXCL10, activating effector CD8⁺ T cells, thereby enhancing anti-tumor immunity. Finally, the promising therapeutic potential of targeting specific chemokine signaling axes, such as CCL2/CCR2 and CXCL10/CXCR3, was discussed as a strategy to improve the efficacy of cancer immunotherapy.

MSCs are an important component of the TME and play a key role in tumor progression. Based on existing in vitro studies, this research aims to investigate the role of mesenchymal stem cells in the EMT of HNSCC and its related mechanisms.

According to the PRISMA guidelines, we systematically searched PubMed, Embase, and Web of Science databases for relevant in vitro studies up to May 6, 2024. Two trained researchers independently performed literature screening, data extraction, and quality assessment, with cross-checking of results. Any disagreements were resolved through discussion or by consulting a third party. Meta-analysis was conducted using Stata 17 software.

A total of 8 in vitro studies were included, involving OSCC, NPC, and TSCC. The meta-analysis results indicate that MSC intervention may be associated with a reduction in the expression of epithelial markers and an increase in mesenchymal markers and related transcription factors in cancer cells, implying a potential role for MSCs in promoting EMT in vitro. Furthermore, a preliminary review of the underlying molecular mechanisms suggests that this process may involve the potential regulation of multiple signaling pathways, including NF-κB, PI3K/Akt/mTOR, IL-6R/JAK/STAT3, CXCL8/CXCR2, TGF-β/Smad, and FGF19-FGFR4.

The existing in vitro evidence suggests that mesenchymal stem cells may exhibit a potential to promote EMT in HNSCC, potentially regulating tumor progression through multiple signaling pathway networks and providing new potential targets for future therapies targeting the TME. However, more high-quality, standardized in vivo and in vitro studies are needed to further validate the related mechanisms and therapeutic potential.