Overexpression of CCL-20 and CXCL-8 genes enhances tumor escape and resistance to cemiplimab, a programmed cell death protein-1 (PD-1) inhibitor, in patients with locally advanced and metastatic cutaneous squamous cell carcinoma.

Cemiplimab has demonstrated relevant clinical activity in cutaneous squamous cell carcinoma (cSCC) but mechanisms of primary and acquired resistance to immunotherapy are still unknown. We collected clinical data from locally advanced and/or metastatic cSSC patients treated with cemiplimab in two Italian University centers. In addition, gene expression analysis by using Nanostring Technologies platform to evaluate 770 cancer- and immune-related genes on 20 tumor tissue samples (9 responders and 11 non-responders to cemiplimab) was performed.

Advances in preclinical TCR characterization: leveraging cell avidity to identify functional TCRs.

T-cell therapy has emerged as an effective approach for treating viral infections and cancers. However, a significant challenge is the selection of T-cell receptors (TCRs) that exhibit the desired functionality. Conventionally techniques, such as peptide sensitivity measurements and cytotoxicity assays, provide valuable insights into TCR potency but are labor-intensive.

All for one: Collaboration between dermatologist, radiation oncologist and radiologist in the clinical management of "difficult to treat" non melanoma skin cancer.

This series introduces the clinical management of difficult-to-treat non-melanoma skin cancers (NMSCs) through a multidisciplinary approach, emphasizing the integration of dermoscopy and Ultra high-frequency ultrasound (UHFUS) for accurate diagnosis and treatment planning, particularly in cases referred for radiotherapy (RT). Dermoscopy aids in diagnosing both pigmented and non-pigmented skin lesions, guiding treatment margins and reducing the benign-to-malignant biopsy ratio. UHFUS provides valuable insights into tumor size, depth, and vascularity, complementing clinical evaluations and assisting in RT planning.

A chimeric antigen receptor-based cellular safeguard mechanism for selective depletion of engineered T cells.

Adoptive immunotherapy based on chimeric antigen receptor (CAR)-engineered T cells has exhibited impressive clinical efficacy in treating B-cell malignancies. However, the potency of CAR-T cells carriethe potential for significant on-target/off-tumor toxicities when target antigens are shared with healthy cells, necessitating the development of complementary safety measures. In this context, there is a need to selectively eliminate therapeutically administered CAR-T cells, especially to revert long-term CAR-T cell-related side effects.

Magnetic Resonance Imaging Evaluation of Bone Metastases Treated with Radiotherapy in Palliative Intent: A Multicenter Prospective Study on Clinical and Instrumental Evaluation Assessment Concordance (MARTE Study).

Metastasis to bone is a common occurrence among epithelial tumors, with a high incidence rate in the Western world. As a result, bone lesions are a significant burden on the healthcare system, with a high morbidity index. These injuries are often symptomatic and can lead to functional limitations, which in turn cause reduced mobility in patients.

Long-term persistence and functionality of adoptively transferred antigen-specific T cells with genetically ablated PD-1 expression.

Engagement of the inhibitory T cell receptor programmed cell death protein 1 (PD-1) associates with dysfunctional states of pathogen- or tumor-specific T cells. Accordingly, systemic antibody-mediated blockade of PD-1 has become a central target for immunotherapies but is also associated with severe toxicities due to loss of peripheral tolerance. Therefore, selective ablation of PD-1 expression on adoptively transferred T cells through direct genetic knockout (KO) is currently being explored as an alternative therapeutic approach.

The role of brain radiotherapy for EGFR- and ALK-positive non-small-cell lung cancer with brain metastases: a review.

Non-small cell lung cancer (NSCLC) is frequently complicated by central nervous system (CNS) metastases affecting patients' life expectancy and quality. At the present clinical trials including neurosurgery, radiotherapy (RT) and systemic treatments alone or in combination have provided controversial results. CNS involvement is even more frequent in NSCLC patients with EGFR activating mutations or ALK rearrangement suggesting a role of target therapy in the upfront treatment in place of loco-regionals treatments (i.

Role of Cardiac Biomarkers in Non-Small Cell Lung Cancer Patients.

Treatment-induced cardiac toxicity represents an important issue in non-small cell lung cancer (NSCLC) patients, and no biomarkers are currently available in clinical practice. A novel and easy-to-calculate marker is the quantitative analysis of calcium plaque in the coronary, calculated on CT. It is called the Agatston score (or CAD score).

RBD-Based ELISA and Luminex Predict Anti-SARS-CoV-2 Surrogate-Neutralizing Activity in Two Longitudinal Cohorts of German and Spanish Health Care Workers.

The ability of antibodies to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important correlate of protection. For routine evaluation of protection, however, a simple and cost-efficient anti-SARS-CoV-2 serological assay predictive of serum neutralizing activity is needed. We analyzed clinical epidemiological data and blood samples from two cohorts of health care workers in Barcelona and Munich to compare several immunological readouts for evaluating antibody levels that could be surrogates of neutralizing activity.

Diffusion-weighted imaging and apparent diffusion coefficient mapping of head and neck lymph node metastasis: a systematic review.

Aim: Head and neck squamous cell cancer (HNSCC) is the ninth most common tumor worldwide. Neck lymph node (LN) status is the major indicator of prognosis in all head and neck cancers, and the early detection of LN involvement is crucial in terms of therapy and prognosis. Diffusion-weighted imaging (DWI) is a non- invasive imaging technique used in magnetic resonance imaging (MRI) to characterize tissues based on the displacement motion of water molecules.

Gene Signatures of T-Cell Activation Can Serve as Predictors of Functionality for SARS-CoV-2-Specific T-Cell Receptors.

The importance of T cells in controlling SARS-CoV-2 infections has been demonstrated widely, but insights into the quality of these responses are still limited due to technical challenges. Indeed, understanding the functionality of the T-cell receptor (TCR) repertoire of a polyclonal antigen-specific population still requires the tedious work of T-cell cloning or TCR re-expression and subsequent characterization. In this work, we show that it is possible to discriminate highly functional and bystander TCRs based on gene signatures of T-cell activation induced by recent peptide stimulation.

Non-Oncological Radiotherapy: A Review of Modern Approaches.

Despite being usually delivered in oncological patients, radiotherapy can be used as a successful treatment for several non-malignant disorders. Even though this use of radiotherapy has been scarcely investigated since the 1950s, more recent interest has actually shed the light on this approach. Thus, the aim of this narrative review is to analyze the applications of non-oncological radiotherapy in different disorders.

SARS-CoV-2 CD8 T cell killing assays using replicating viruses and transgenic antigens.

The quality of an antigen-specific CD8 T cell repertoire is crucial for the clearance of intracellular pathogens, in particular for viral infections. Here, we describe killing assays to determine the function of CD8 T cells engineered with SARS-CoV-2-specific T cell receptors in a near-physiological system for antigen presentation. We detail the use of target cells either infected with replicating SARS-CoV-2 virus or engineered with SARS-CoV-2 open reading frames.

Signatures of recent activation identify a circulating T cell compartment containing tumor-specific antigen receptors with high avidity.

T cell receptor (TCR) avidity is assumed to be a major determinant of the spatiotemporal fate and protective capacity of tumor-specific T cells. However, monitoring polyclonal T cell responses with known TCR avidities in vivo over space and time remains challenging. Here, we investigated the fate and functionality of tumor neoantigen-specific T cells with TCRs of distinct avidities in a well-established, reductionist preclinical tumor model and human patients with melanoma.

CMV seropositivity is a potential novel risk factor for severe COVID-19 in non-geriatric patients.

Background: COVID-19 has so far affected more than 250 million individuals worldwide, causing more than 5 million deaths. Several risk factors for severe disease have been identified, most of which coincide with advanced age. In younger individuals, severe COVID-19 often occurs in the absence of obvious comorbidities.

ChipCytometry for multiplexed detection of protein and mRNA markers on human FFPE tissue samples.

In this protocol, we describe the use of ChipCytometry to combine RNA hybridization and antibody staining for multiplexed tissue imaging of human formalin-fixed and paraffin-embedded tissue samples. The advantages of ChipCytometry are long-term storage for re-interrogation and advanced image quality by high dynamic range imaging of staining and background. A titrated pretreatment of tissue samples bypasses challenges because of the retrieval of antigens on coverslips and achieves an optimal staining quality at the minimal expense of tissue integrity.

Multiplexed imaging and automated signal quantification in formalin-fixed paraffin-embedded tissues by ChipCytometry.

Deciphering the spatial composition of cells in tissues is essential for detailed understanding of biological processes in health and disease. Recent technological advances enabled the assessment of the enormous complexity of tissue-derived parameters by highly multiplexed tissue imaging (HMTI), but elaborate machinery and data analyses are required. This severely limits broad applicability of HMTI.

Global k -rates of polyclonal T-cell populations merge subclonal avidities and predict functionality.

The avidity of TCRs for peptide-major histocompatibility complexes (pMHCs) is a governing factor in how T cells respond to antigen. TCR avidity is generally linked to T-cell functionality and there is growing evidence for distinct roles of low and high avidity T cells in different phases of immune responses. While physiological immune responses and many therapeutic T-cell products targeting infections or cancers consist of polyclonal T-cell populations with a wide range of individual avidities, the role of T-cell avidity is usually investigated only in monoclonal experimental settings.

Recruitment of highly cytotoxic CD8 T cell receptors in mild SARS-CoV-2 infection.

T cell immunity is crucial for control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has been studied widely on a quantitative level. However, the quality of responses, in particular of CD8 T cells, has only been investigated marginally so far. Here, we isolate T cell receptor (TCR) repertoires specific for immunodominant SARS-CoV-2 epitopes restricted to common human Leukocyte antigen (HLA) class I molecules in convalescent individuals.

Delta radiomics: a systematic review.

Background: Radiomics can provide quantitative features from medical imaging that can be correlated with various biological features and clinical endpoints. Delta radiomics, on the other hand, consists in the analysis of feature variation at different acquisition time points, usually before and after therapy. The aim of this study was to provide a systematic review of the different delta radiomics approaches.

Phantosmia, Parosmia, and Dysgeusia Are Prolonged and Late-Onset Symptoms of COVID-19.

Deficiencies in smell and taste are common symptoms of COVID-19. Quantitative losses are well surveyed. This study focuses on qualitative changes such as phantosmia (hallucination of smell), parosmia (alteration of smell), and dysgeusia (alteration of taste) and possible connections with the adaptive immune system.