ADA/CD26 axis increases intra-tumor PD-1CD28CD8 T-cell fitness and affects NSCLC prognosis and response to ICB.

Improving cancer immunotherapy efficacy hinges on identifying key T-cell populations critical for tumor control and response to Immune Checkpoint Blockade (ICB). We have recently reported that while the co-expression of PD-1 and CD28 is associated with impaired functionality in peripheral blood, it significantly enhances T-cell fitness in the tumor site of non-small cell lung cancer (NSCLC) patients. To uncover the underlying mechanisms, we explored the role of CD26, a key player in T-cell activation through its interaction with adenosine deaminase (ADA), a crucial intra/extracellular enzyme able to neutralize local adenosine (ADO).

Tumoral and stromal hMENA isoforms impact tertiary lymphoid structure localization in lung cancer and predict immune checkpoint blockade response in patients with cancer.

Background: Tertiary Lymphoid Structures (TLS) correlate with positive outcomes in patients with NSCLC and the efficacy of immune checkpoint blockade (ICB) in cancer. The actin regulatory protein hMENA undergoes tissue-specific splicing, producing the epithelial hMENA linked to favorable prognosis in early NSCLC, and the mesenchymal hMENAΔv6 found in invasive cancer cells and pro-tumoral cancer-associated fibroblasts (CAFs). This study investigates how hMENA isoforms in tumor cells and CAFs relate to TLS presence, localization and impact on patient outcomes and ICB response.

CD28/PD1 co-expression: dual impact on CD8 T cells in peripheral blood and tumor tissue, and its significance in NSCLC patients' survival and ICB response.

Background: Immune checkpoint blockade (ICB) has significantly prolonged survival of non-small cell lung cancer (NSCLC) patients, although most patients develop mechanisms of resistance. Recently single-cell RNA-sequencing (scRNA-Seq) revealed a huge T-cell phenotypic and (dys)functional state variability. Accordingly, T-cell exhaustion is recognized as a functional adaptation, with a dynamic progression from a long-lived "pre-exhausted stem-like progenitor" to a "terminally exhausted" state.

A cytofluorimetric assay to evaluate T cell polyfunctionality.

The magnitude and the quality of T-cell response are critical endpoints in the immune-monitoring of cancer patients. The release of cytokines and lytic factors by T cells operate in each phase of the cancer immunity cycle. The simultaneous cytokine production, defined as T-cell polyfunctionality, is a dynamic state of different T-cell subsets and may represent a surrogate biomarker of response to immune-mediated therapies.

Survival and prognostic factors in cats with restrictive cardiomyopathy: a review of 90 cases.

Objectives: Large studies focusing on restrictive cardiomyopathy (RCM) in the cat are scarce. The aims of this retrospective study were to describe epidemiological characteristics and to analyse prognostic factors affecting survival in cats with RCM.

Methods: The clinical archives of the Gran Sasso Veterinary Clinic (Milan, Italy) and of the cardiology unit of the Department of Veterinary Medicine (University of Milan, Italy) from 1997-2015 were reviewed for all cats diagnosed with RCM based on an echocardiographic examination (left atrial/biatrial enlargement, normal left ventricle wall thickness, normal or mildly decreased systolic function and restrictive left ventricle filling pattern with pulsed Doppler echocardiography).