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Exosomes are a type of extracellular vesicle whose study has grown exponentially in recent years. This led to the understanding that these structures, far from being inert waste by-products of cellular functioning, are active players in intercellular communication mechanisms, including in the interactions between cancer cells and the immune system. The deep comprehension of the crosstalk between tumors and the immune systems of their hosts has gained more and more importance, as immunotherapeutic techniques have emerged as viable options for several types of cancer. In this review, we present a comprehensive, updated, and elucidative review of the current knowledge on the functions played by the exosomes in this crosstalk. The roles of these vesicles in tumor antigen presentation, immune activation, and immunosuppression are approached as the relevant interactions between exosomes and the complement system. The last section of this review is reserved for the exploration of the results from the first phase I to II clinical trials of exosomes-based cell-free cancer vaccines.

Os neurónios dopaminérgicos da área tegmentar ventral (VTA) desempenham um papel fundamental no processamento de estímulos recompensadores e aversivos, e a sua resposta a estímulos relevantes é modelada de modo significativo por aferentes que têm origem nos núcleos colinérgicos do tronco cerebral. O envelhecimento está associado a um declínio na actividade dopaminérgica e a uma resposta reduzida ao reforço positivo. Neste estudo foram usadas técnicas estereológicas para analisar, em ratos adultos e velhos, os neurónios dopaminérgicos e a inervação colinérgica da VTA, e as populações colinérgicas dos núcleos pedunculopontino (PPT) e tegmentar laterodorsal (LDT), as quais constituem a única fonte da inervação colinérgica da VTA. Na VTA, não houve variações relacionadas com a idade no número e no volume dos neurónios imunorreactivos para a tirosina hidroxilase (TH), mas a densidade das varicosidades colinérgicas estava reduzida nos ratos velhos. O número total de neurónios imunorreactivos para a colina acetiltransférase (ChAT) no PPT e no LDT permaneceu inalterado, mas o volume somático desses neurónios estava aumentado nos ratos velhos. Estes resultados sugerem que a disfunção do sistema colinérgico pode contribuir para a deterioração associada à idade do sistema de recompensa cerebral. / Dopamine neurons in the ventral tegmental area (VTA) play a main role in processing both rewarding and aversive stimuli, and their response to salient stimuli is significantly shaped by afferents originating in the brainstem cholinergic nuclei. Aging is associated with a decline in dopaminergic activity and reduced response to positive reinforcement. We have used stereological techniques to examine, in adult and aged rats, the dopaminergic neurons and the cholinergic innervation of the VTA, and the cholinergic populations of the pedunculopontine tegmental (PPT) and laterodorsal tegmental (LDT) nuclei, which are the only source of cholinergic inputs to the VTA. In the VTA, there were no age-related variations in the number and size of tyrosine hydroxylase (TH)-immunoreactive neurons, but the density of cholinergic varicosities was reduced in aged rats. The total number of choline acetyltransferase (ChAT)-immunoreactive neurons in the PPT and LDT were unchanged, but their somas were hypertrophied in aged rats. Our results suggest that dysfunction of the cholinergic system might contribute for the age-associated deterioration of the brain reward system.

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