Mirvetuximab soravtansine is an antibody-drug conjugate approved for the treatment of folate receptor alpha-expressing ovarian cancer and is associated with ocular adverse events. Patients treated with mirvetuximab soravtansine often develop moderate to severe keratopathy, requiring topical steroids. Recent studies suggest a higher incidence of cataract formation than initially reported. This case series describes the rapid development of visually significant cataracts in 3 patients receiving mirvetuximab therapy.

Three female patients undergoing treatment with mirvetuximab soravtansine for platinum-resistant serous ovarian cancer experienced significant visual decline after 11, 18, and 19 treatment cycles, in 1 case progressing from 20/25 to counting fingers in both eyes within 10 weeks. All patients had baseline ophthalmic examinations and were treated with prophylactic topical corticosteroids to mitigate corneal complications. Despite standard management, each patient developed bilateral posterior subcapsular cataracts with substantial loss of visual acuity. Patients underwent sequential or same-day bilateral cataract extraction without complication. Postoperatively, all patients regained their baseline vision, and oncologic therapy was continued.

Rapidly progressing posterior subcapsular cataracts may occur in patients receiving prolonged mirvetuximab soravtansine therapy and may reflect drug-related toxicity, steroid exposure, or a synergistic interaction. Given that these patients did not develop cataracts until later cycles, ophthalmologic monitoring may be warranted beyond the duration specified in current treatment protocols. Early recognition and cataract surgery can restore vision without requiring cessation of oncologic therapy.

Gambogic acid (GA) shows potent inhibitory activity against various malignancies. However, achieving precise targeted delivery and spatiotemporal control of drug release at tumor sites remains a significant challenge. This study aimed to develop a hyaluronic acid (HA)-modified, redox-responsive drug delivery system based on a methoxy polyethylene glycol-linked GA prodrug (mPEG-ss-GA).

The amphiphilic prodrug, mPEG-ss-GA, was synthesized by conjugating GA to methoxy polyethylene glycol (mPEG) via a disulfide linkage. Subsequently, it spontaneously self-assembled with HA in an aqueous medium to form HA-modified mPEG-ss-GA micelles (HA/mPEG-ss-GA-M). The physicochemical properties of the micelles, including particle size, zeta potential, morphology, and in vitro release profiles, were systematically characterized. Cellular uptake in human non-small cell lung cancer cells (A549) was visualized using fluorescence microscopy. Furthermore, the in vitro pro-apoptotic effects were quantified using an Annexin V-propidium iodide (PI) binding assay. Finally, the in vivo anti-tumor efficacy was evaluated in a subcutaneous xenograft tumor model.

The HA/mPEG-ss-GA-M micelles exhibited an average particle size of 251 nm with a zeta potential of -17.36 mV. The system demonstrated glutathione (GSH)-triggered drug release, with release kinetics that aligned well with the Higuchi model. In vitro studies revealed that HA/mPEG-ss-GA-M significantly enhanced cellular uptake, induced apoptosis, and suppressed cell migration. In vivo experiments showed that HA/mPEG-ss-GA-M achieved a tumor volume inhibition rate of 54.09%, compared to 29.56% for free GA.

HA/mPEG-ss-GA-M is a promising drug delivery system for targeted non-small cell lung cancer therapy and offers precise and efficient treatment options.

The Radiological Evaluation Score for Bone Tumors (REST) system is a radiographic tool of excellent diagnostic accuracy with a score of >3, being 100% predictive of malignant bone lesions. The present study is designed to externally validate the REST tool among reviewers of varying clinical experience and against their clinical gestalt.

The REST system was externally validated on the radiographs of primary bone tumors with a confirmed histopathological diagnosis. Three reviewers (MDH, HRS, MSH) independently reviewed 104 radiographs of primary bone tumors using the REST system to provide cumulative and individual radiographic factor score. Three separate reviewers (ARJ, RHL, SCH) independently reviewed radiographs based on their clinical gestalt and rated them as either benign or malignant bone lesions. The institutional histopathological report was considered the reference standard for the validation. The characteristics of diagnostic accuracy within and between the groups were measured by sensitivity and specificity and receiver operator characteristic curves. The inter-group and intra-group observer correlation was calculated with 95% confidence intervals.

104 radiographs of bone lesions with equal incidence of benign and malignant lesions were included in this study. The sensitivity and specificity of the REST Score group for diagnosing a malignant bone lesion were 80.8% and 84.6%, whereas the sensitivity and specificity of the clinical gestalt group were 63.5% and 90.4%, and this difference was statistically significant (p = 0.017). However, the difference in area under the curve 0.058 (-0.028 to 0.143) between the REST score group and clinical gestalt group, however, was not statistically significant p = 0.187. The reviewers in the REST group had greater interobserver reliability when compared to that of the clinical gestalt group [0.738 (0.637-0.815) vs. 0.446 (0.336-0.557)].

The REST is a radiographic tool of considerable diagnostic accuracy that can be used as a key step in the systematic evaluation of bone lesions.

Despite significantly improving outcomes in non-small cell lung cancer (NSCLC), neoadjuvant chemoimmunotherapy (NCIT) fails to achieve a major pathological response (MPR) in over 40% of patients. Consequently, the early identification of non-responders prior to treatment initiation remains a critical unmet clinical need.

In this study, we performed single-cell RNA sequencing (scRNA-seq) on pre-treatment NSCLC tissue samples and integrated data from two public databases to identify signaling pathways associated with poor treatment response. Key findings were subsequently validated using multiplex immunofluorescence (mIF), and the predictive value of identified molecules was finally assessed in our cohort and GEO datasets.

Among the 83 patients, 23/57 (40.35%) of these radiological responders failed to achieve MPR. Data analysis revealed activation of stress-related signaling pathways in cancer-associated fibroblasts (CAFs) and T cells from nMPR patients, with elevated expression of stress-related markers, including BAG3 and IFITM2. MIF confirmed that BAG3⁺IFITM2⁺ CAFs and BAG3⁺CD8⁺ T cells were spatially adjacent and significantly more abundant in nMPR patients. In our cohort and the two public databases, the BAG3⁺ CAF-T Cell Neighborhood was significantly more abundant in the nMPR group compared to the MPR group (p<0.05). In the MPR group, there was no significant difference in BAG3⁺ CAF-T Cell Neighborhood between the radiological PR and non-PR subgroups. The AUC values of BAG3⁺IFITM2⁺ CAFs, BAG3⁺CD8⁺ T cells, and the BAG3⁺ CAF-T Cell Neighborhood were 0.84 [95%CI: 0.746-0.931], 0.72 [95%CI: 0.603-0.835], and 0.87 [95%CI: 0.787-0.948], respectively. The OS and DFS of the BAG3⁺ CAF-T Cell Neighborhood high group are significantly decreased than that of the low group (p<0.05). The level of BAG3⁺ CAF-T Cell Neighborhood outperformed other two indicators in predicting non-response to NCIT. Consistent results were observed in GSE126044 and GSE135222.

The BAG3⁺ CAF-T Cell Neighborhood may serve as a biomarker for predicting non-response to NCIT in NSCLC, with significant potential to inform clinical decision-making.

Multiple Myeloma (MM) is the third most common hematological malignancy worldwide. Despite advancements in available therapies, MM remains incurable for most patients, mainly due to the early relapse and eventual resistance to therapy, underlining the need for novel drugs. Among these, multi-specific antibodies (MsAbs) have emerged as promising agents. Multi-specific immune cell-engaging antibodies, such as bi-specific, and tri-specific are designed to recognize two or more antigens on the same or distinct cells. These antibodies could promote cancer cell clearance by engaging both myeloma cells and cytotoxic immune cells such as T and Natural killer (NK) cells and macrophages (M). Currently, four bi-specific T cell engagers (teclistamab, elranatamab, talquetamab and linvoseltamab) are approved for refractory or relapsed MM patients (RRMM). While these therapies have demonstrated promising results in achieving deep remissions in RRMM, primary resistance occurs in about one-third of patients. Initially, immune engager research focused only on T cells due to their crucial anti-cancer role, but more recently, interest has expanded to NK cells and M for broader therapeutic potential. To date, several NK and M engaging MsAbs with mainly bi-specific and tri-specific formats are in clinical or preclinical evaluation for improving MM patients' response and reduce treatment related toxicity. This review discusses the recent advancement in T, NK and M engaging MsAbs in treating MM, including immunological background, mechanisms of action, relevant clinical and preclinical advancements and challenges. Moreover, we discuss the advantages and drawbacks of the different immune cell engagers. Furthermore, we review recent studies investigating the clinical and molecular determinants of resistance along with the latest predictive or prognostic biomarkers of response to MsAbs. Finally, we explore novel strategies to enhance MsAbs efficacy and reduce their toxicity, providing long-term disease control and improving survival in MM patients.

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers and is characterised by an immunologically "cold" microenvironment that limits responses to immunotherapy. This review focuses on interleukin-6 (IL-6), produced by stromal and immune cells as well as PDAC cells, as a central driver of immune evasion via JAK-STAT3 signalling. We outline how SOCS3 silencing in tumour cells inverts the IL-6-IDO relationship seen in dendritic cells, generating an autocrine IDO-Kyn-AhR-IL-6-STAT3 feedforward loop. We further describe IL-6-mediated stabilisation of PD-L1, sustained PD-1 expression on CD8⁺ T cells, and ST6GAL1-driven hypersialylation that activates Siglec glyco-immune checkpoints. In addition, we examine the IL-6-Blimp-1-IL-10 axis and its reprogramming of dendritic cell and T cell compartments. Given the repeated failure of IL-6(R) blockade in clinical trials, we contrast these outcomes with the more encouraging signals from RAS-targeted strategies. We propose rational IL-6-integrated combinations with upstream oncogenic targeting may represent an unrealised frontier for this disease.

Oral squamous cell carcinoma (OSCC) represents a common malignancy characterized by significant morbidity and mortality rates, highlighting the critical necessity for novel therapeutic approaches. Consequently, investigating differentially expressed genes linked to inflammation and pyroptosis may identify potential prognostic biomarkers and therapeutic targets.

To address this research gap, our study utilized an extensive bioinformatics approach by analyzing the Cancer Genome Atlas Head and Neck Squamous Cell Carcinoma (TCGA-HNSC) dataset through differential expression analysis to identify genomic features associated with OSCC. Subsequent analyses included Gene Ontology and pathway enrichment assessments, along with survival analyses using Cox regression models, to evaluate the prognostic significance of the identified differentially expressed genes. Furthermore, immune infiltration analysis and somatic mutation assessments were conducted to elucidate the relationship between immune cell types and key prognostic genes. Additionally, copy number variation analysis was performed to highlight genomic alterations associated with immune-related and prognostic-related differentially expressed genes(DEGs).

Our analysis identified a total of 3,495 differentially expressed genes, among which 53 immune-related and prognosis-related differentially expressed genes demonstrated a significant correlation with the prognosis of OSCC. Immune infiltration analysis further revealed the presence of 28 immune cell types within OSCC samples, with a notable prevalence of activated CD8 T cells and regulatory T cells, underscoring their association with critical prognostic genes. Additionally, pathway analysis highlighted the activation of cytokine signaling pathways and their associations with processes relevant to systemic lupus erythematosus. A prognostic risk model derived from these findings effectively stratified patients based on overall survival, identifying four key genes-CTSG,HKDC1,PTX3 and SPP1-as crucial prognostic indicators. This analysis may uncover potential prognostic biomarkers and therapeutic targets.

This study established a novel OSCC prognostic risk model based on inflammation- and pyroptosis-related interactive genes. CTSG, HKDC1, PTX3 and SPP1 were validated as independent prognostic biomarkers, and the risk score was closely associated with tumor microenvironment features, metabolic activity, and therapeutic sensitivity. This work may provides substantial references for the exploration of novel biomarkers for OSCC treatment and facilitates clinical decision-making.

CD244, expressed in the tumor microenvironment (TME), is associated with impaired function of natural killer (NK) and T cells; however, its role in diffuse large B-cell lymphoma (DLBCL) remains poorly understood. This study aimed to elucidate the immunological significance and regulatory mechanisms of CD244 in DLBCL.

Using single-cell and bulk RNA sequencing, we analyzed CD244 expression patterns, its major intracellular adaptor molecules, and correlations with immune checkpoints, metabolic alterations, and immune activity. The clinical and biological implications of CD244 expression, including associations with clinicopathological characteristics, TME composition, prognosis, and response to immune checkpoint blockade (ICB) therapy, were investigated by integrating single-cell and bulk RNA sequencing, immunohistochemistry, and reverse transcription-quantitative polymerase chain reaction. Intercellular communication networks, key transcription factors, and somatic mutations were further evaluated to uncover regulatory mechanisms.

NK cells were the primary CD244-expressing population in DLBCL, co-overexpressing PDCD1, CTLA4, LAG3, TIGIT, PTGER4, and CD160. EAT2 was identified as CD244's predominant intracellular adaptor, suggesting that CD244-associated inhibitory signaling may contribute to metabolic dysregulation and immune dysfunction in NK cells. Elevated CD244 expression correlated with an immunosuppressive TME, worse clinicopathological features, poorer outcomes, and increased potential responsiveness to ICB. Furthermore, CD244 expression may be regulated by STAT3 activation in NK cells and ASXL3 mutations in tumor cells via the BTLA-TNFRSF14 pathway.

This study highlights the critical role of CD244 in NK cell dysfunction and DLBCL progression, providing a promising target for optimizing immunotherapy.

Human papillomavirus (HPV)-associated cancers provide a unique model for understanding the paradox of viral antigenicity and tumor immune escape. Although viral oncoproteins such as E6 and E7 generate non-self antigens, many HPV-associated tumors persist under immune pressure and show heterogeneous responses to immune checkpoint blockade. This discrepancy reflects a process in which persistent HPV infection and malignant transformation remodel innate immune sensing, interferon (IFN) signaling, antigen presentation, and the tumor microenvironment. These changes impair dendritic cell activation and cytotoxic immune priming while promoting chronic inflammation, myeloid polarization, T-cell exhaustion, and PD-1/PD-L1-mediated adaptive immune resistance. In this review, we discuss how HPV-associated cancers subvert antiviral innate immunity and how these processes contribute to immune evasion. We further highlight therapeutic strategies aimed at restoring antiviral antitumor immunity, including immune checkpoint blockade, STING agonists, therapeutic HPV vaccines, radiotherapy-based combinations, TGF-β pathway inhibition, and biomarker-guided treatment approaches. Understanding the links among viral pathogenesis, innate immune remodeling, and checkpoint evasion may support more rational immunotherapy combinations for HPV-associated malignancies.

Multifocal nodular oncocytic hyperplasia (MNOH) of the salivary glands is a rare benign condition that can mimic both benign and malignant neoplasms, posing significant diagnostic challenges. Its bilateral and multifocal presentation is exceptionally uncommon. We present a unique case initially interpreted as bilateral Warthin tumor, later redefined as bilateral acinic cell carcinoma and finally reclassified as MNOH after comprehensive histopathological and immunohistochemical evaluation, and review the literature.

A 71-year-old woman presented with a long-standing mass in the left mandibular angle region. Fine-needle aspiration was compatible with Warthin tumor. MRI revealed a well-defined, partially cystic, enhancing lesion in the left parotid gland and a similar nodule in the contralateral gland. A left parotid tumorectomy with synchronous submandibular nodule excision was performed, both initially reported as acinic cell carcinoma (DOG1 positive). Subsequent left total parotidectomy showed multifocal acinic cell carcinoma, with negative FISH for CRTC1/MAML2, ruling out mucoacinar carcinoma. Contralateral MRI revealed multiple nodules with perfusion curves suggestive of Warthin tumor. Right parotidectomy revealed multifocal oncocytic hyperplasia with oncocytomas and extensive clear cell change. Immunohistochemistry demonstrated DOG1 apical positivity, but focal p63 expression and SOX10 negativity favored oncocytic hyperplasia/oncocytoma. Clinicopathologic correlation confirmed the diagnosis of bilateral MNOH.

This case illustrates the pitfalls in diagnosing oncocytic lesions, where radiology, cytology, and even immunohistochemistry may mimic acinic cell carcinoma. The review of published cases confirms the rarity of bilateral MNOH and highlights the importance of correlating morphology, immunoprofiles, and clinical context.

MNOH should be considered in the differential diagnosis of bilateral parotid lesions to avoid overtreatment. Recognition of its histological spectrum, including clear cell and oncocytoma-like features, is essential for accurate diagnosis.