RESUMO
Pancreatic cancer (PC) is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide. However, due to its complexity, it ranks 7th in the list of the most lethal cancers worldwide. The pathogenesis of PC involves several complex processes, including familial genetic factors associated with risk factors such as obesity, diabetes mellitus, chronic pancreatitis, and smoking. Mutations in genes such as KRAS, TP53, and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and, consequently, cancer. In this context, some therapies are used for PC, one of which is immunotherapy, which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy efficiency. It is therefore clear that the tumor microenvironment (TME) has a huge impact on the resistance process, since cellular and non-cellular elements create an immunosuppressive environment, characterized by a dense desmoplastic stroma with cancer-associated fibroblasts, pancreatic stellate cells, extracellular matrix, and immunosuppressive cells. Linked to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells, resulting in a shortage of CD8+ T cells and limited expression of activation markers such as interferon-gamma. In this way, finding new strategies that make it possible to manipulate resistance mechanisms is necessary. Thus, techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance, the use of genetic manipulation in specific regions, such as microRNAs, the modulation of extrinsic and intrinsic factors associated with T cells, and, above all, therapeutic models that combine these modulation techniques constitute the promising future of PC therapy. Thus, this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating this process, resulting in a more efficient therapy for cancer patients and, consequently, a reduction in the lethality of this aggressive cancer.
RESUMO
Coronavirus disease-19 (COVID-19) has become a pandemic, being a global health concern since December 2019 when the first cases were reported. Severe acute respiratory syndrome coronavirus 2, the COVID-19 causal agent, is a ß-coronavirus that has on its surface the spike protein, which helps in its virulence and pathogenicity towards the host. Thus, effective and applicable diagnostic methods to this disease come as an important tool for the management of the patients. The use of the molecular technique PCR, which allows the detection of the viral RNA through nasopharyngeal swabs, is considered the gold standard test for the diagnosis of COVID-19. Moreover, serological methods, such as enzyme-linked immunosorbent assays and rapid tests, are able to detect severe acute respiratory syndrome coronavirus 2-specific immunoglobulin A, immunoglobulin M, and immunoglobulin G in positive patients, being important alternative techniques for the diagnostic establishment and epidemiological surveillance. On the other hand, reverse transcription loop-mediated isothermal amplification also proved to be a useful diagnostic method for the infection, mainly because it does not require a sophisticated laboratory apparatus and has similar specificity and sensitivity to PCR. Complementarily, imaging exams provide findings of typical pneumonia, such as the ground-glass opacity radiological pattern on chest computed tomography scanning, which along with laboratory tests assist in the diagnosis of COVID-19.
