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    Considering therapy-induced senescence as a mechanism of tumour dormancy contributing to disease recurrence. British journal of cancer The capability of tumour cells to escape from therapy-induced senescence, as well as cell-non-autonomous functions of senescence, support the premise that senescence could serve as one pathway to tumour dormancy (among others that include quiescence and diapause) that is permissive for disease recurrence. Consequently, the pharmacologic targeting of senescent tumour cells could mitigate the risk for cancer resurgence, thereby enhancing the therapeutic efficacy of cancer chemotherapy. 10.1038/s41416-022-01787-6
    Extricating human tumour immune alterations from tissue inflammation. Nature Immunotherapies have achieved remarkable successes in the treatment of cancer, but major challenges remain. An inherent weakness of current treatment approaches is that therapeutically targeted pathways are not restricted to tumours, but are also found in other tissue microenvironments, complicating treatment. Despite great efforts to define inflammatory processes in the tumour microenvironment, the understanding of tumour-unique immune alterations is limited by a knowledge gap regarding the immune cell populations in inflamed human tissues. Here, in an effort to identify such tumour-enriched immune alterations, we used complementary single-cell analysis approaches to interrogate the immune infiltrate in human head and neck squamous cell carcinomas and site-matched non-malignant, inflamed tissues. Our analysis revealed a large overlap in the composition and phenotype of immune cells in tumour and inflamed tissues. Computational analysis identified tumour-enriched immune cell interactions, one of which yields a large population of regulatory T (T) cells that is highly enriched in the tumour and uniquely identified among all haematopoietically-derived cells in blood and tissue by co-expression of ICOS and IL-1 receptor type 1 (IL1R1). We provide evidence that these intratumoural IL1R1 T cells had responded to antigen recently and demonstrate that they are clonally expanded with superior suppressive function compared with IL1R1 T cells. In addition to identifying extensive immunological congruence between inflamed tissues and tumours as well as tumour-specific changes with direct disease relevance, our work also provides a blueprint for extricating disease-specific changes from general inflammation-associated patterns. 10.1038/s41586-022-04718-w
    Regulation of intrinsic and extrinsic metabolic pathways in tumour-associated macrophages. The FEBS journal Tumour-associated macrophages (TAMs) are highly plastic and are broadly grouped into two major functional states, namely the pro-inflammatory M1-type and the pro-tumoural M2-type. Conversion of the functional states of TAMs is regulated by various cytokines, chemokines growth factors and other secreted factors in the microenvironment. Dysregulated metabolism is a hallmark of cancer. Emerging evidence suggests that metabolism governs the TAM differentiation and functional conversation in support of tumour growth and metastasis. Aside from the altered metabolism reprogramming in TAMs, extracellular metabolites secreted by cancer, stromal and/or other cells within the tumour microenvironment have been found to regulate TAMs through passive competition for metabolite availability and direct regulation via receptor/transporter-mediated signalling reaction. In this review, we focus on the regulatory roles of different metabolites and metabolic pathways in TAM conversion and function. We also discuss if the dysregulated metabolism in TAMs can be exploited for the development of new therapeutic strategies against cancer. 10.1111/febs.16465
    Pulmonary tumour embolism and lymphangitis carcinomatosa: a case report and review of the literature. Journal of cardiothoracic surgery BACKGROUND:Pulmonary tumour embolism and lymphangitis carcinomatosa are complications of malignancy that may mimic the clinical presentation of pulmonary embolism. CASE PRESENTATION:We present the case of a 52-year-old male patient with acute-onset right ventricular strain and dyspnoea with elevated D-dimer and without signs of pulmonary embolism on computed tomography pulmonary angiogram (CTPA) and ventilation/perfusion scintigraphy. The patient died eleven days after initial presentation. The diagnosis of pulmonary tumour embolism and lymphangitis carcinomatosa due to carcinoma of unknown origin was made post-mortem by immunohistochemical examination. CONCLUSION:Pulmonary tumour embolism and lymphangitis carcinomaosa are complications of malignancy and potential causes of acute right ventricular strain. Radiological signs are unspecific and the clinical course usually fatal. These differential diagnoses should be considered in patients with acute right ventricular strain, dyspnoea and positive D-dimer if there are no signs of pulmonary embolism on CTPA. 10.1186/s13019-022-01832-8
    Clinical relevance of tumour-associated macrophages. Nature reviews. Clinical oncology In the past decade, substantial advances have been made in understanding the biology of tumour-associated macrophages (TAMs), and their clinical relevance is emerging. A particular aspect that is becoming increasingly clear is that the interaction of TAMs with cancer cells and stromal cells in the tumour microenvironment enables and sustains most of the hallmarks of cancer. Therefore, manipulation of TAMs could enable improved disease control in a substantial fraction of patients across a large number of cancer types. In this Review, we examine the diversity of TAMs in various cancer indications and how this heterogeneity is being revisited with the advent of single-cell technologies, and then explore the current knowledge on the functional roles of different TAM states and the prognostic and predictive value of TAM-related signatures. We also review agents targeting TAMs that are currently being or will soon be tested in clinical trials, and how manipulations of TAMs can improve existing anticancer treatments. Finally, we discuss how TAM-targeting approaches could be further integrated into routine clinical practice, considering a precision oncology approach and viewing TAMs as a dynamic population that can evolve under treatment pressure. 10.1038/s41571-022-00620-6