From ex vivo to in vivo chimeric antigen T cells manufacturing: new horizons for CAR T-cell based therapy.

In the past decades, Chimeric Antigen Receptor (CAR)-T cell therapy has achieved remarkable success, leading to the approval of six therapeutic products for haematological malignancies. Recently, the therapeutic potential of this therapy has also been demonstrated in non-tumoral diseases. Currently, the manufacturing process to produce clinical-grade CAR-T cells is complex, time-consuming, and highly expensive.

Nephrotoxicity in locally advanced head and neck cancer: when the end justifies the means to preserve nutritional status during chemoradiation.

Cisplatin is a nephrotoxic agent able to damage renal function both in acute and chronic phases. Radiotherapy concomitant with cisplatin 100 mg/m given once every 3 weeks is the curative standard of care for locally advanced head and neck cancer. A prospective evaluation of a wide range of biochemical and anthropometrical parameters, handgrip strength, risk of malnutrition, visual analogue scale of appetite, and body composition was performed before, during, and after concomitant chemoradiotherapy in 60 consecutive patients affected by locally advanced head and neck cancer.

Association Between Thyrotoxicosis and Cerebral Venous Thrombosis.

Thyrotoxicosis appears to be a predisposing factor for cerebral venous thrombosis (CVT), which is a rare but important cause of stroke in young adults. The presentation of CVT is highly variable, ranging from a history of headaches (in the majority of cases) to deep coma, with the latter requiring invasive neurosurgical decompression. Although the long-term outcomes of CVT are favorable, multicenter cohort studies have shown that death may occur in up to 4% of cases in the acute phase and 8-10% of cases in the long term.

The impact of nutritional intervention on quality of life and outcomes in patients with head and neck cancers undergoing chemoradiation.

Introduction: Chemoradiotherapy in head and neck cancer patients has a curative intent but often deteriorates nutritional status leading to sarcopenia and cachexia.

Methods: In this observational and single-centered study, a prospective evaluation of several biochemical and anthropometrical parameters, weight loss, handgrip strength, visual analogue scale of appetite, questionnaires associated with malnutrition & quality of life and body composition (obtained by Bioelectrical Impedance Vector Analysis) was performed before and after high-dose cisplatin chemotherapy combined with radiotherapy in 60 patients affected by head and neck cancer. Oral nutritional supplements were used to reach the correct number of daily calories and proteins.

Water and Electrolyte Content in Hypertension in the Skin (WHYSKI) in Primary Aldosteronism.

Background: Primary aldosteronism (PA), the most common curable salt-dependent form of arterial hypertension, features renal K loss and enhanced Na reabsorption. We investigated whether the electrolyte, water, and TonEBP (tonicity-responsive enhancer binding protein)/ (nuclear factor of activated T cells 5) content is altered in the skin of patients with PA and corrected by surgical cure.

Methods: We obtained skin biopsies from 80 subjects: 49 consecutive patients with PA, optimally treated with a mineralocorticoid receptor antagonist; 6 essential hypertensives; and 25 normotensive controls.

From Tumor Macroenvironment to Tumor Microenvironment: The Prognostic Role of the Immune System in Oral and Lung Squamous Cell Carcinoma.

Background: The interplay between cancer cells and the immune system is crucial in cancer progression and treatment. In this regard, the tumor immune microenvironment and macroenvironment, marked by systemic inflammation markers and TILs, could be considered key prognostic factors in tumors, including oral and lung squamous cell carcinoma.

Methods: We conducted a retrospective clinical study on patients with Oral Squamous Cell Carcinoma (OSCC) and Lung Squamous Cell Carcinoma (LUSCC), examining stages, comorbidities, treatments, and outcomes.

Moderate physical activity during neoadjuvant chemotherapy in breast cancer patients: effect on cancer-related inflammation and pathological complete response-the Neo-Runner study.

Background: Physical activity (PA) reduces the risk of developing breast cancer (BC) and mortality rate in BC patients starting PA after diagnosis. Immunomodulation is considered responsible for these effects. However, limited data exist on the immunomodulation induced by moderate PA (mPA) during neoadjuvant chemotherapy (NACT).

Effects of a Personalized Diet on Nutritional Status and Renal Function Outcome in Nephrectomized Patients with Renal Cancer.

Nutritional therapy (NT) based on a controlled protein intake represents a cornerstone in managing chronic kidney disease (CKD). However, if a CKD patient is at the same time affected by cancer, oncologists and nutritionists tend to suggest a dietary regimen based on high protein intake to avoid catabolism and malnutrition. International guidelines are not clear when we consider onco-nephrological patients and, as a consequence, no clinical shared strategy is currently applied in clinical practice.

Baseline Values of Circulating IL-6 and TGF-β Might Identify Patients with HNSCC Who Do Not Benefit from Nivolumab Treatment.

Background: The immunotherapy of head and neck cancer induces a limited rate of long-term survivors at the cost of treating many patients exposed to toxicity without benefit, regardless of PD-L1 expression. The identification of better biomarkers is warranted. We analyzed a panel of cytokines, chemokines and growth factors, hereinafter all referred to as 'cytokines', as potential biomarkers in patients with head and neck cancer treated with nivolumab.

Baseline Cytokine Profile Identifies a Favorable Outcome in a Subgroup of Colorectal Cancer Patients Treated with Regorafenib.

Metastatic colorectal cancer is frequently associated with poor clinical conditions that may limit therapeutic options. Regorafenib is a small molecule approved for the treatment of metastatic colorectal cancer, but it is hampered by significative toxicities. Moreover, only a relatively limited number of patients benefit from the treatment.

Clinical Significance of Molecular Subtypes in Western Advanced Gastric Cancer: A Real-World Multicenter Experience.

In recent years, the molecular subtyping of gastric cancer has led to the identification of novel clinically relevant biomarkers as well as promising therapeutic targets. In parallel, the advent of checkpoint inhibitors has expanded treatment options beyond conventional chemotherapy. Compelling evidence has shown unprecedented efficacy results for anti-PD1-based therapies in the molecular subgroups of dMMR/MSI-h, EBV+ and PD-L1 CPS+ patients, to the point that these are granted approval for gastric cancer adenocarcinoma (AGC) in several countries.

Why Oncologists Should Feel Directly Involved in Persuading Patients with Head and Neck Cancer to Quit Smoking.

Introduction: Among the risk factors for squamous cell carcinoma of the head and neck, smoking is still the most important today. Several studies agree on the effect of smoking on tumor microenvironment, while the definition of former smokers and the time of smoking cessation on biologic effect differs among papers.

Methods: We conducted a narrative review on smoking effects in HNSCC.

The Role of Cytokinome in the HNSCC Tumor Microenvironment: A Narrative Review and Our Experience.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer. In locally advanced (LA) HNSCC, a multidisciplinary approach consisting of surgery followed by chemoradiation (CRT) or definitive CRT is the mainstay of treatment. In recurrent metastatic (R/M), HNSCC immune checkpoint inhibitors (ICIs) with or without chemotherapy represent the new first-line option.

How Chemotherapy Affects the Tumor Immune Microenvironment: A Narrative Review.

Chemotherapy is much more effective in immunocompetent mice than in immunodeficient ones, and it is now acknowledged that an efficient immune system is necessary to optimize chemotherapy activity and efficacy. Furthermore, chemotherapy itself may reinvigorate immune response in different ways: by targeting cancer cells through the induction of cell stress, the release of damage signals and the induction of immunogenic cell death, by targeting immune cells, inhibiting immune suppressive cells and/or activating immune effector cells; and by targeting the host physiology through changes in the balance of gut microbiome. All these effects acting on immune and non-immune components interfere with the tumor microenvironment, leading to the different activity and efficacy of treatments.

Effect of Eribulin on Angiogenesis and the Expression of Endothelial Adhesion Molecules.

Background/aim: Tumor vasculature is an important component of the tumor microenvironment and deeply affects anticancer immune response. Eribulin is a non-taxane inhibitor of the mitotic spindle. However, off-target effects interfering with the tumor vasculature have been reported.

Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: TALAPRO-2 phase III study design.

PARP inhibitors in combination with androgen receptor-targeted therapy have demonstrated potential in the treatment of metastatic castration-resistant prostate cancer (mCRPC). Here, we describe the design and rationale of the multinational, phase III, two-part TALAPRO-2 study comparing talazoparib plus enzalutamide versus placebo plus enzalutamide as a first-line treatment for patients with mCRPC with or without DNA damage response (DDR) alterations. This study has two co-primary end points: radiographic progression-free survival (rPFS) by blinded independent clinical review in all-comers (cohort 1) and in patients with DDR alterations (cohort 2).

Circulating Cytokines in Metastatic Breast Cancer Patients Select Different Prognostic Groups and Patients Who Might Benefit from Treatment beyond Progression.

Cancer induces immune suppression to overcome its recognition and eradication by the immune system. Cytokines are messengers able to modulate immune response or suppression. There is great interest in the evaluation of their changes during treatment in order to identify their relationship with clinical outcome.

Inotuzumab Ozogamicin for Relapsed/Refractory Acute Lymphoblastic Leukemia in the INO-VATE Trial: CD22 Pharmacodynamics, Efficacy, and Safety by Baseline CD22.

Purpose: We assessed the relationship between cluster of differentiation-22 (CD22) expression and outcomes of inotuzumab ozogamicin versus standard of care (SC) in INO-VATE (NCT01564784).

Patients And Methods: Adults with relapsed/refractory B-cell precursor CD22-positive (by local or central laboratory) acute lymphoblastic leukemia were randomized to inotuzumab ozogamicin ( = 164) or SC ( = 162). Outcomes were analyzed by baseline CD22 positivity (percentage of leukemic blasts CD22 positive, ≥90% vs.

Exploratory analysis of circulating cytokines in patients with metastatic breast cancer treated with eribulin: the TRANSERI-GONO (Gruppo Oncologico del Nord Ovest) study.

Background: Anticancer drugs can interact with the tumour microenvironment and their effects could be exploited to favour anticancer immune response. Eribulin contributes to tumour vasculature remodelling and transforming growth factor β (TGF-β) modulation in experimental models and in humans. We performed a prospective, translational, exploratory analysis of the levels of circulating cytokines at different time points in patients with metastatic breast cancer treated with eribulin.

Circulating cytokines and outcome in metastatic colorectal cancer patients treated with regorafenib.

Background: Regorafenib is an oral small-molecule multikinase inhibitor approved in third or later line of treatment for patients with metastatic colorectal cancer (mCRC). Regorafenib has shown significant benefits in overall survival and progression free survival in two phase III trials compared to placebo in patients with mCRC who had progressed on previous therapy.

Aim: To identify an immune profile that might specifically correlate with the outcome in patients treated with regorafenib.

Inotuzumab ozogamicin versus standard of care in Asian patients with relapsed/refractory acute lymphoblastic leukemia.

Inotuzumab ozogamicin (InO) is a targeted treatment for adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). InO was previously studied in INO-VATE, an international, open-label, randomized phase 3 trial comparing InO against standard of care (SoC). In the present subgroup analysis, we evaluated outcomes in the 55 Asian patients who were randomized in INO-VATE (31 InO and 24 SoC).

Efficacy and safety analysis by age cohort of inotuzumab ozogamicin in patients with relapsed or refractory acute lymphoblastic leukemia enrolled in INO-VATE.

Background: Inotuzumab ozogamicin (InO) has demonstrated efficacy and tolerability in patients aged 18 to 78 years with relapsed/refractory acute lymphoblastic leukemia (ALL) in the INO-VATE trial. This subset analysis compared the efficacy and safety of InO in younger and older patients.

Methods: Intent-to-treat analyses of morphologic responses and overall survival (OS) included 326 randomized patients, and safety assessments included 307 patients receiving 1 or more doses of the study treatment.

Synthesis and biological evaluation of novel thiazole- VX-809 hybrid derivatives as F508del correctors by QSAR-based filtering tools.

The most common CF mutation, F508del, impairs the processing and gating of CFTR protein. This deletion results in the improper folding of the protein and its degradation before it reaches the plasma membrane of epithelial cells. Present correctors, like VX809 only induce a partial rescue of the mutant protein.