Malignant pleural mesothelioma (MPM) is a rare and fatal disease of the pleural lining. Up to 80% of the MPM cases are linked to asbestos exposure. Even though its use has been banned in the industrialized countries, the cases continue to increase. MPM is a lethal cancer, with very little survival improvements in the last years, mirroring very limited therapeutic advances. Platinum-based chemotherapy in combination with pemetrexed and surgery are the standard of care, but prognosis is still unacceptably poor with median overall survival of approximately 12 months. The genomic landscape of MPM has been widely characterized showing a low mutational burden and the impairment of tumor suppressor genes. Among them, BAP1 and BLM are present as a germline inactivation in a small subset of patients and increases predisposition to tumorigenesis. Other studies have demonstrated a high frequency of mutations in DNA repair genes. Many therapy approaches targeting these alterations have emerged and are under evaluation in the clinic. High-throughput technologies have allowed the detection of more complex molecular events, like chromotripsis and revealed different transcriptional programs for each histological subtype. Transcriptional analysis has also paved the way to the study of tumor-infiltrating cells, thus shedding lights on the crosstalk between tumor cells and the microenvironment. The tumor microenvironment of MPM is indeed crucial for the pathogenesis and outcome of this disease; it is characterized by an inflammatory response to asbestos exposure, involving a variety of chemokines and suppressive immune cells such as M2-like macrophages and regulatory T cells. Another important feature of MPM is the dysregulation of microRNA expression, being frequently linked to cancer development and drug resistance. This review will give a detailed overview of all the above mentioned features of MPM in order to improve the understanding of this disease and the development of new therapeutic strategies.

Pleural mesothelioma (PM) is an aggressive tumor with few therapeutic options. Although patients with epithelioid PM (ePM) survive longer than non-epithelioid PM (non-ePM), heterogeneity of tumor response in ePM is observed. The role of the tumor immune microenvironment (TIME) in the development and progression of PM is currently considered a promising biomarker. A few studies have used high-throughput technologies correlated with TIME evaluation and morphologic and clinical data. This study aimed to identify different morphological, immunohistochemical, and transcriptional profiles that could potentially predict the outcome. A retrospective multicenter cohort of 129 chemonaive PM patients was recruited. Tissue slides were reviewed by dedicated pathologists for histotype classification and immunophenotype of tumor-infiltrating lymphocytes (TILs) and lymphoid aggregates or tertiary lymphoid structures (TLS). ePM (n = 99) survivors were further classified into long (>36 months) or short (<12 months) survivors. RNAseq was performed on a subset of 69 samples. Distinct transcriptional profiling in long and short ePM survivors was found. An inflammatory background with a higher number of B lymphocytes and a prevalence of TLS formations were detected in long compared to short ePM survivors. These results suggest that B cell infiltration could be important in modulating disease aggressiveness, opening a pathway for novel immunotherapeutic approaches.

Background: Patients of malignant mesothelioma (MM) and their caregivers face significant physical and psychological challenges. The purpose of the present study is to examine the emotional impact after the diagnosis of MM in a group of patients and familial caregivers in a National Priority Contaminated Site (NPCS). Methods: A sample of 108 patients and 94 caregivers received a sociodemographic/clinical questionnaire, the Beck Depression Inventory II, the Davidson Trauma Scale, the Coping Orientation to the Problems Experienced—New Italian Version, and the Defense style questionnaire. The risk of depressive and post-traumatic stress disorder (PTSD) symptoms in relation to the strategies of coping and defense mechanisms was estimated in patients and caregivers separately by logistic regression models. Results: For patients, a high risk of depression was associated with high usage of Defense Style Questionnaire (DSQ) Isolation (OR: 53.33; 95% CI: 3.22–882.30; p = 0.01) and DSQ Somatization (OR: 16.97; 95% CI: 1.04–275.90; p = 0.05). Other significant risks emerged for some coping strategies and some defenses regarding both depression and trauma in patients and caregivers. Conclusions: This research suggests that for both patients and caregivers unconscious adaptive processes have a central role in dealing with overwhelming feelings related to the disease.

Growing evidence highlights the pivotal role of the gut microbiota in cancer development, progression, response to therapy, and survivorship. Diet plays a central role in shaping gut microbiota composition, influencing the immune system and overall host health. Plant-based diets and the Mediterranean diet promote health-associated microbial communities that increase the production of several metabolic-end products, including short-chain fatty acids that support mucosal barrier integrity, anti-inflammatory effects, and modulation of the immunity of the host. Conversely, Western dietary patterns promote cancer progression and negatively impact the response to standard treatments. Furthermore, gut microbiota influences the effectiveness of cancer therapies, including chemotherapy, radiotherapy and, mainly, immunotherapy. Modulating microbial species, their metabolites, or their activities in the cancer microenvironment through dietary interventions, common or engineered probiotics, prebiotics, postbiotics, antibiotics or fecal microbial transplant are emerging as promising strategies for cancer prevention and tailored management in survivorship. In this review, we explore the intricate interplay between diet, gut microbiota, and cancer, focusing on how specific microbial communities’ impact therapeutic outcomes, and the challenges in the modulation of the microbiota environment through several interventions, including diet. This emerging paradigm paves the way for integrating nutrition and microbiota-targeted strategies as innovative tools in the context of precision medicine.

Asbestos (all forms, including chrysotile, crocidolite, amosite, tremolite, actinolite, and anthophyllite) is carcinogenic to humans and causally associated with mesothelioma and cancer of the lung, larynx, and ovary. It is one of the carcinogens most diffuse in the world, in workplaces, but also in the environment and is responsible for a very high global cancer burden. A large number of countries, mostly with high-income economies, has banned the use of asbestos which, however, is still widespread in low- and middle-income countries. It remains, thus, one of the most common occupational and environmental carcinogens worldwide. Italy issued an asbestos ban in 1992, following the dramatic observation of a large increase in mortality from mesothelioma and other asbestos-related diseases in exposed workers and also in subjects with non-occupational exposure. A mesothelioma registry was also organized and still monitors the occurrence of mesothelioma cases, conducting a case-by-case evaluation of asbestos exposure. In this report, we describe two Italian communities, Casale Monferrato and Broni, that faced an epidemic of mesothelioma resulting from the production of asbestos cement and the diffuse environmental exposure; we present the activity and results of the Italian mesothelioma registry (ReNaM), describe the risk-communication activities at the local and national level with a focus on international cooperation and also describe the interaction between mesothelioma registration and medical services specialized in mesothelioma diagnosis and treatment in an area at high risk of mesothelioma. Finally, we assess the potential application of the solutions and methods already developed in Italy in a city in Colombia with high mesothelioma incidence associated with the production of asbestos-cement materials and the presence of diffuse environmental asbestos pollution.

In traditional medical education, learners are mostly trained to diagnose and treat patients through supervised practice. Artificial Intelligence and simulation techniques can complement such an educational practice. In this paper, we present GLARE-Edu, an innovative system in which AI knowledge-based methodologies and simulation are exploited to train learners “how to act” on patients based on the evidence-based best practices provided by clinical practice guidelines. GLARE-Edu is being developed by a multi-disciplinary team involving physicians and AI experts, within the AI-LEAP (LEArning Personalization of AI and with AI) Italian project. GLARE-Edu is domain-independent: it supports the acquisition of clinical guidelines and case studies in a computer format. Based on acquired guidelines (and case studies), it provides a series of educational facilities: (i) navigation, to navigate the structured representation of the guidelines provided by GLARE-Edu, (ii) automated simulation, to show learners how a guideline would suggest to act, step-by-step, on a specific case, and (iii) (self)verification, asking learners how they would treat a case, and comparing step-by-step the learner’s proposal with the suggestions of the proper guideline. In this paper, we describe GLARE-Edu architecture and general features, and we demonstrate our approach through a concrete application to the melanoma guideline and we propose a preliminary evaluation.