A First-in-Human Phase I Clinical Study with MVX-ONCO-1, a Personalized Active Immunotherapy, in Patients with Advanced Solid Tumors.

Unlabelled: Over two decades, most cancer vaccines failed clinical development. Key factors may be the lack of efficient priming with tumor-specific antigens and strong immunostimulatory signals. MVX-ONCO-1, a personalized cell-based cancer immunotherapy, addresses these critical steps utilizing clinical-grade material to replicate a successful combination seen in experimental models: inactivated patient's own tumor cells, providing the widest cancer-specific antigen repertoire and a standardized, sustained, local delivery over days of a potent adjuvant achieved by encapsulated cell technology.

Identification of clinically relevant T cell receptors for personalized T cell therapy using combinatorial algorithms.

A central challenge in developing personalized cancer cell immunotherapy is the identification of tumor-reactive T cell receptors (TCRs). By exploiting the distinct transcriptomic profile of tumor-reactive T cells relative to bystander cells, we build and benchmark TRTpred, an antigen-agnostic in silico predictor of tumor-reactive TCRs. We integrate TRTpred with an avidity predictor to derive a combinatorial algorithm of clinically relevant TCRs for personalized T cell therapy and benchmark it in patient-derived xenografts.

Rare Synchronous Lung Cancers in a Nonsmoker with Epidermal Growth Factor Receptor and Mesenchymal-Epithelial Transition Alterations: A Case Report.

Introduction: Lung cancer is the second most common cancer; however, synchronous lung cancer is rare and challenging to treat.

Case Presentation: We report the case of an 80-year-old female patient who presented with two lung lesions with primary tumor characteristics, which revealed squamous cell carcinoma and synchronous adenocarcinoma after histological sampling. Next-generation sequencing (NGS) analysis revealed a MET Exon 14 skipping mutation in squamous cell carcinoma and an epidermal growth factor receptor mutation in adenocarcinoma.

Characteristics of long-survivor metastatic melanoma after polychemotherapy and interferon: a retrospective study.

Background: The development of immunotherapy and tyrosine kinase inhibitors dramatically improved the prognosis of metastatic melanoma. Consequently, chemotherapy is now rarely used. Here, we describe the characteristics of long-surviving patients with metastatic melanoma treated with immunochemotherapy.

Paraneoplastic Autoimmune Limbic Encephalitis Associated with an Atypical Carcinoid Tumor of the Lung: A Case Report.

We report the case of a patient with a history of an atypical lung carcinoid tumor who developed a rapidly progressive memory impairment. The clinical presentation as well as brain MRI, cerebrospinal fluid, and laboratory tests led to the diagnosis of seronegative paraneoplastic autoimmune limbic encephalitis. To the best of our knowledge, this is the first case in literature of such association.

Unnecessary thyroid surgery rate for suspicious nodule in the absence of molecular testing.

Background: Molecular tests for suspicious thyroid nodules decrease rates of unnecessary surgeries but are not widely used due to reimbursement issues. The aim of this study was to assess the rate of unnecessary surgery performed in real-life setting for Bethesda III, IV and V nodules in the absence of molecular testing.

Method: This is a single-center retrospective study of consecutive patients undergoing fine needle aspiration cytology (FNAC) with rapid on-site evaluation between January 2017 and December 2021.

PET/MR Imaging in Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) can either be examined with hybrid PET/MR imaging systems or sequentially, using PET/CT and MR imaging. Regardless of the acquisition technique, the superiority of MR imaging compared to CT lies in its potential to interrogate tumor and surrounding tissues with different sequences, including perfusion and diffusion. For this reason, PET/MR imaging is preferable for the detection and assessment of locoregional residual/recurrent HNSCC after therapy.

A monoclonal antibody targeting nonjunctional claudin-1 inhibits fibrosis in patient-derived models by modulating cell plasticity.

Tissue fibrosis is a key driver of end-stage organ failure and cancer, overall accounting for up to 45% of deaths in developed countries. There is a large unmet medical need for antifibrotic therapies. Claudin-1 (CLDN1) is a member of the tight junction protein family.

Atypical pulmonary phaeohyphomycosis due to Aureobasidium spp. - case report and brief literature review.

We report on a case of probable invasive Auerobasidium spp. pulmonary infection in a patient with myelodysplastic syndrome. The patient was successfully treated with liposomal amphotericin B monotherapy, with transition to orally administered isavuconazole.

Rosai-Dorfman disease presenting as stridor and hoarseness in a young female patient.

Rosai-Dorfman disease is a non-Langherans cell histiocytosis typically revealed by lymphadenopathy. Extranodal involvement occurs in 43% and most commonly involves the head and neck, skin, and bones. Few reports have described laryngeal lesions.

The first comprehensive genomic characterization of rectal squamous cell carcinoma.

Background: Rectal cancers represent 35% of colorectal cancers; 90% are adenocarcinomas, while squamous cell carcinoma accounts for 0.3% of them. Given its rarity, little is known concerning its pathogenesis, molecular profile and therapeutic management.

Complications of congenital portosystemic shunts: liver tumors are affected by shunt severity, but pulmonary and neurocognitive associations are not.

Background And Purpose: Congenital portosystemic shunts (CPSS) are associated with multisystem complications, with the most common being liver tumors. The purpose of this study is to investigate the incidence of complications of CPSS, and to determine the natural history of liver tumors and their relationship with shunt closure.

Methods: Single-center retrospective cohort study of patients with CPSS referred from 1990 to 2020.

MR Imaging of Laryngeal and Hypopharyngeal Cancer.

State-of-the-art MR imaging of the larynx and hypopharynx with high-resolution surface coils, parallel imaging techniques, and DWI has several advantages over CT for assessing submucosal tumor spread, in particular neoplastic involvement of the paraglottic space, laryngeal cartilages, and extralaryngeal soft tissues. Current diagnostic MR imaging criteria based on a combination of distinct imaging features on morphologic sequences combined with DWI allow improved discrimination between tumor, peritumoral inflammation, and fibrosis and, ultimately, an increased precision for submucosal tumor delineation, which is a key prerequisite for tailored treatment options. Multiparametric MR imaging with DWI has a higher diagnostic performance than CT.

Primary Extra-Osseous Ewing Sarcoma of the Thyroid: A Case Report and Review of the Literature.

Extra-osseous Ewing sarcoma (ES) is a rare and aggressive malignant tumor found in a variety of organs. Primary ES of the thyroid is exceedingly rare and few cases have been documented to date. We describe the case of a 54-year old woman with a history of breast carcinoma in whom a unique hypermetabolic left thyroid nodule was identified during a follow-up PET-CT scan.

Resident Kupffer cells and neutrophils drive liver toxicity in cancer immunotherapy.

Immunotherapy is revolutionizing cancer treatment but is often restricted by toxicities. What distinguishes adverse events from concomitant antitumor reactions is poorly understood. Here, using anti-CD40 treatment in mice as a model of T1-promoting immunotherapy, we showed that liver macrophages promoted local immune-related adverse events.

The Impact of Variant Allele Frequency in EGFR Mutated NSCLC Patients on Targeted Therapy.

EGFR mutations represent the most common currently targetable oncogenic driver in non-small cell lung cancer. There has been tremendous progress in targeting this alteration over the course of the last decade, and third generation tyrosine kinase inhibitors offer previously unseen survival rates among these patients. Nonetheless, a better understanding is still needed, as roughly a third of patients do not respond to targeted therapy and there is an important heterogeneity among responders.

Tristetraprolin Promotes Hepatic Inflammation and Tumor Initiation but Restrains Cancer Progression to Malignancy.

Background & Aims: Tristetraprolin (TTP) is a key post-transcriptional regulator of inflammatory and oncogenic transcripts. Accordingly, TTP was reported to act as a tumor suppressor in specific cancers. Herein, we investigated how TTP contributes to the development of liver inflammation and fibrosis, which are key drivers of hepatocarcinogenesis, as well as to the onset and progression of hepatocellular carcinoma (HCC).

The GLP-1R agonist liraglutide limits hepatic lipotoxicity and inflammatory response in mice fed a methionine-choline deficient diet.

Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disorder related to type 2 diabetes (T2D). The disease can evolve toward nonalcoholic steatohepatitis (NASH), a state of hepatic inflammation and fibrosis. There is presently no drug that effectively improves and/or prevents NAFLD/NASH/fibrosis.

The impact of short-term machine perfusion on the risk of cancer recurrence after rat liver transplantation with donors after circulatory death.

Hypothermic and normothermic ex vivo liver perfusions promote organ recovery after donation after circulatory death (DCD). We tested whether these perfusions can reduce the risk of hepatocellular carcinoma (HCC) recurrence in a 1h-DCD syngeneic transplantation model, using Fischer F344 rats. DCD grafts were machine perfused for 2h with hypothermic perfusion (HOPE) or normothermic perfusion (NORMO), and transplanted.

Multi-technique comparison of atherogenic and MCD NASH models highlights changes in sphingolipid metabolism.

Lipotoxicity is a key player in the pathogenesis of nonalcoholic steatohepatitis (NASH), a progressive subtype of nonalcoholic fatty liver disease (NAFLD). In the present study, we combine histological, transcriptional and lipidomic approaches to dissociate common and specific alterations induced by two classical dietary NASH models (atherogenic (ATH) and methionine/choline deficient (MCD) diet) in C57BL/6J male mice. Despite a similar degree of steatosis, MCD-fed mice showed more pronounced liver damage and a worsened pro-inflammatory and pro-fibrogenic environment than ATH-fed mice.

Macrofollicular Variant of Follicular Thyroid Carcinoma: A Rare Underappreciated Pitfall in the Diagnosis of Thyroid Carcinoma.

Follicular-patterned thyroid nodules predominantly composed of macrofollicular structures without nuclear atypia are generally regarded as benign (i.e., hyperplastic nodules or follicular adenomas).

Portal venous deprivation in patients with portosystemic shunts and its effect on liver tumors.

Aims: To outline the use of radiological investigations in patients with congenital portosystemic shunts (CPS) and to assess the degree of portal venous deprivation in relation to the development of liver tumors.

Methods: Single center retrospective cohort study of all patients with CPS referred from 1990 to 2016. Radiological investigations were reviewed for the presence of intrahepatic portal veins.