Repeated tumor contact leaves more behind than simple CAR-T exhaustion. This study by Gu et al. (https://doi.org/10.1084/jem.20252564) shows that chronic antigen exposure impairs a Rab5-dependent endocytic program, allowing trogocytosed antigen to accumulate, functional CAR to decline, and fratricide to increase.

The impact of deep learning (DL) reconstruction and segmentation on MRI radiomics stability has not been fully assessed.

To investigate the effects of acquisition, reconstruction, and segmentation on the reproducibility and variability of radiomic features in abdominal MRI.

Prospective.

37 volunteers (22 men; mean age ± standard deviation, 37.4 ± 11.0 years).

3.0-T; axial turbo spin echo T2-weighted image, and fat-suppressed T2-weighted image using a half-Fourier acquisition single-shot turbo spin echo technique, each acquired four times with conventional or accelerated techniques, reconstructed with standard or DL algorithms.

Regions of interest were automatically generated by a DL neural network for liver, spleen, and right and left kidneys, followed by manual correction. We extracted 107 features using PyRadiomics after z-score normalization.

The reproducibility between acquisitions, reconstructions, and segmentations was evaluated using intraclass correlation coefficient (ICC) and concordance correlation coefficient (CCC). The variability among the four scans was assessed by coefficient of variation (CV) and quartile coefficient of dispersion (QCD). p < 0.05 was considered significant.

The mean ICC (0.518-0.608; 0.606-0.681) and CCC (0.515-0.603; 0.601-0.680) values were low for both manual and automatic segmentation regardless of image acquisition and reconstruction, using conventional acquisition with standard reconstruction as reference. The mean ICC (0.535-0.713) and CCC (0.531-0.714) values were low between manual and automatic segmentation, regardless of image acquisition and reconstruction. The median CV (10.0%-17.5%; 8.9%-15.5%) and QCD (5.3%-8.5%; 5.1%-8.3%) values were moderate but still adequate for both manual and automatic segmentation among different scans.

Given the substantial impact of accelerated acquisition and DL reconstruction on the robustness of radiomics features in abdominal MRI, caution should be exercised when utilizing images with different acquisition and reconstruction techniques in radiomics analysis. The automatic segmentation cannot replace manual segmentation due to insufficient robustness of radiomics features.

2.

Stage 1.

Gastric cancer (GC) and esophagogastric junction cancer (EGJC) impose a severe global burden, with traditional treatments plagued by poor efficacy, high toxicity, and chemoresistance. Claudin 18.2 (CLDN18.2), a highly tissue-specific target, is abnormally overexpressed in GC/EGJC with limited overlap with HER2 positivity or PD-L1 CPS ≥5, making it ideal for precision therapy. Zolbetuximab, a CLDN18.2-targeted ADC, exerts anti-tumor effects via "targeted binding-endocytosis-MMAE release", reducing systemic toxicity versus traditional chemotherapy. Pivotal trials (MONO, FAST, SPOTLIGHT/GLOW, ILUSTRO) confirmed its monotherapy efficacy and superior PFS/OS when combined with chemotherapy (EOX, mFOLFOX6, CAPOX) in CLDN18.2-positive (≥70% staining), HER2-negative advanced GC/EGJC patients, with manageable safety. SPOTLIGHT/GLOW laid the foundation for its first-line approval. Post-approval, it may expand to other CLDN18.2-positive tumors and neoadjuvant/adjuvant therapy, with combination regimen optimization. However, MMAE's long-term cumulative toxicity, uncertain safety in special populations, and rare severe adverse reactions require real-world validation. This review systematically summarizes zolbetuximab's research progress, providing a reference for clinical application and future studies.

Signet ring cells are extremely rare in primary endometrial carcinomas with a limited number of reported cases. We report a series of 5 endometrioid-type endometrial carcinomas with signet ring cells, the largest reported series in the literature to date. The patients ranged in age from 53 to 89 yr (mean: 72), and all presented with postmenopausal bleeding. Four of the tumors were FIGO grade 3, and 1 FIGO grade 2, and the FIGO stages were IA, IB, IIIA, IIIB, and IIIC1. The percentage of signet ring cells ranged from 10% to 30% of the tumor, and the signet ring cells were confined to solid areas of the neoplasm. All tumors were positive with estrogen receptor (ER) (4 diffuse, 1 focal); p53 immunohistochemistry was wild-type in 4 and diffuse mutation-type in 1. Three neoplasms were mismatch repair (MMR) deficient (loss of MLH1/PMS2) on immunohistochemistry. Molecular testing revealed a POLE pathogenic variant with an associated ultramutated phenotype in one of the MMR-proficient tumors and a TP53 mutation in the tumor exhibiting mutation-type p53 staining (this was also MMR proficient on immunohistochemistry). Using The Cancer Genome Atlas (TCGA) molecular classification, tumors were POLE mutated (n=1), MMR deficient (n=3), and p53 abnormal (n=1). On follow-up, 4 patients were alive with no evidence of disease (4-24 mo follow-up), and 1 patient died 7 mo after diagnosis from an unrelated cause. In reporting these neoplasms, we highlight that signet ring cells occasionally occur in primary endometrial carcinomas of endometrioid-type and, although numbers are small, there appears to be an association with MMR deficiency. These tumors have a propensity for high-stage at presentation.

Human cathelicidin peptide LL-37 is encoded by the CAMP gene and plays a key role in innate immunity. It maintains intestinal homeostasis through antibacterial, immunomodulation, and tissue repair functions. This paper reviews the multiple functions of LL-37 in the intestinal-immune axis and its contribution to intestinal immune homeostasis. A large amount of evidence shows that the biological effect of LL-37 is highly dependent on the environmental background, and its effects vary with peptide concentration, receptor binding status, disease stage, and local microenvironment. This article reviews the latest findings of the dual role of LL-37 in inflammatory bowel disease (IBD) and colorectal cancer (CRC), and focuses on the conditional mechanism of the transformation of its activity from protective to pathogenic. We also discuss the interaction between LL-37 and intestinal microbiota, focusing on how microbial signals and host peptides can coordinate to regulate mucosal immunity. At the same time, this article examines the key obstacles to the therapeutic application of LL-37 and its clinical promotion: cytotoxicity, rapid degradation by proteases, and drug resistance. We have further explored new strategies to overcome these challenges in the near future, including peptide engineering, nanocarrier delivery systems, and combined therapy. These findings together position LL-37 at the intersection of intestinal immunity and microbial ecology, providing a theoretical basis for its therapeutic application in IBD, CRC and infectious colitis.

Spitz tumors represent a heterogeneous group of melanocytic neoplasms ranging from benign Spitz nevi to malignant spitzoid melanoma. Atypical Spitz tumors (ASTs) occupy an intermediate category with uncertain biological potential and pose significant diagnostic challenges, particularly in pediatric patients. We report the case of a 14-year-old girl presenting with a recently changing pigmented lesion on the upper back. Histopathologic examination revealed an asymmetric melanocytic proliferation composed predominantly of epithelioid cells with limited mitotic activity and evidence of dermal maturation. Immunohistochemistry showed diffuse Melan-A and SOX10 positivity, retained p16 expression, a gradient HMB45 staining pattern, and negative PRAME expression. For diagnostic purpose, as a part of diagnosis, next-generation sequencing was performed and identified a RET::MXT1 gene fusion in the absence of additional pathogenic mutations or copy number alterations. To our knowledge, this is the first reported case showing this type of RET fusion. This case highlights the importance of an integrated morphologic, immunophenotypic, and molecular diagnostic approach in atypical spitzoid lesions. Identification of an isolated RET fusion supports classification within the Spitz tumor spectrum and provides valuable information for risk stratification and clinical management in pediatric patients.

The convergence of nanotechnology and immunotherapy has ushered in a transformative era in cancer treatment, offering new strategies to overcome pharmacokinetic limitations and immune evasion associated with conventional therapies. While immunotherapy, spanning checkpoint inhibitors, adoptive cell transfer, and cancer vaccines, has revolutionized oncology, its efficacy remains constrained by the immunosuppressive tumor microenvironment (TME), off-target toxicity, and poor biodistribution of therapeutic agents.

This review elucidates how engineered nanoparticles (NPs) are redefining immune-oncology by enabling the precise delivery of immunomodulators, antigens, and genetic payloads to target cells, while reprogramming the TME to convert "cold" tumors into immunogenic "hot" landscapes.

A literature search was conducted using PubMed, Scopus, and Google Scholar. The review was performed in a narrative and non-systematic manner, focusing on studies addressing nanotechnology-enhanced cancer immunotherapy.

We dissect the physicochemical and functional versatility of NPs, emphasizing size-, charge-, and ligand-dependent strategies to enhance lymph node targeting, APC activation, and sustained cargo release. Innovations in metallic, lipid-based, and biomimetic NPs are highlighted, including gold and lipid-based NPs for enhanced immune responses. Furthermore, we explore combinatorial approaches, such as NP-mediated co-delivery of checkpoint inhibitors and chemotherapeutics, which amplify cytotoxic T-cell responses and mitigate systemic toxicity. Clinical advancements, including Nab-Paclitaxel and mRNA-loaded lipid NPs, underscore the translational potential of these platforms, with trials demonstrating improved survival and manageable adverse profiles.

However, challenges persist in optimizing targeting precision, scalability, and long-term safety. Integrating breakthroughs in material science, immunology, and bioengineering, this review charts a roadmap for next-generation nano-immunotherapies, advocating patient-specific designs and multimodal regimens. As the field strides toward clinical maturity, nanotechnology is poised to unlock the full potential of immunotherapy, paving the way for adaptive, immune-guided, and potentially curative cancer therapies.

Not available.

A 4-year-old neutered male cat was presented with a perineal mass extending over the penis. The mass was surgically excised via perineal urethrostomy. Histopathology confirmed a high-grade B-cell lymphoma confined to the penis and extending microscopically to the prepuce. The cat remained disease free for 6 mo before dying of an unknown cause. To the authors' knowledge, this case may represent the first reported instance of a feline lymphoma clinically confined to the penis. Key clinical message: Penile lymphoma, though rare in cats, should be considered in the differential diagnosis for perineal or penile masses. Surgical excision can achieve local control, but prognosis and the role of adjuvant therapy remain uncertain.

Ovarian Steroid Cell Tumors (SCT) are rare sex cord-stromal tumors accounting for less than 0.1% of ovarian neoplasms. Most are hormonally active and present with symptoms of androgen excess. Steroid cell tumor, not otherwise specified (SCT-NOS), represents the majority of cases and carries the greatest malignant potential, although most tumors are benign and cured with surgical excision. Malignant transformation of an initially benign SCT-NOS is rarely reported, and the molecular mechanisms underlying progression remain poorly characterized.

A 41-year-old woman presented with amenorrhea, acne, and hirsutism with markedly elevated testosterone. Imaging demonstrated an 8-cm predominantly solid right adnexal mass. She underwent laparoscopic right salpingo-oophorectomy, and pathology revealed SCT-NOS without histologic features of malignancy. Testosterone normalized postoperatively, and she was managed with surveillance. Three years later, she presented with dyspnea and abdominal pain; imaging demonstrated pleural effusion, ascites, pelvic masses, and peritoneal carcinomatosis. Cytoreductive surgery confirmed malignant SCT-NOS with nuclear atypia, necrosis, and increased mitotic activity. Despite adjuvant carboplatin, paclitaxel, and bevacizumab followed by maintenance therapy, she developed platinum-resistant progression with peritoneal and nodal disease and is currently receiving additional systemic therapy with poor response. Longitudinal next-generation sequencing demonstrated molecular evolution during disease progression. The recurrent, malignant tumor harbored variants in ATM and LZTR1, and the platinum-resistant recurrence showed an additional deletion of STK11. These alterations involve pathways regulating DNA damage response, RAS/MAPK signaling, and cellular growth.

This case presents a rare ovarian steroid cell tumor, not otherwise specified, initially managed with unilateral salpingo-oophorectomy and surveillance given its benign pathologic features. Three years later, the patient developed malignant recurrence. Despite complete surgical cytoreduction and administration of platinum-based adjuvant chemotherapy, the patient experienced disease progression. This case highlights the potential for malignant transformation in benign-appearing SCT-NOS and underscores the importance of counseling patients on the rare risk of recurrence and the need for novel therapeutic strategies in recurrent disease. Integration of clinical, pathologic, and molecular data may improve risk stratification and management of this rare tumor.