Elucidating tumor immunosurveillance and immunoediting: a comprehensive review

The action of the immune system against neoplastic diseases has become one of the main sources of research. The biological pathways of this system are known to contribute in limiting the progression and elimination of the tumor, and are delineated by concepts and mechanisms of immunosurveillance and immunoediting. Immunosurveillance is considered the process by which the immune system recognizes and inhibits the neoplastic process. The concept of immunoediting arises in the sense that immune system is able to shape the antigenic profile of the tumor due to selective pressure, based on the stages of tumor elimination, balance and evasion. The immune response occurs against tumor antigens and changes in the tumor microenvironment, involving different components of the innate immune system, such as T cells, natural Killer cells, B lymphocytes and macrophages. In this sense, knowing these concepts and understanding their respective mechanisms becomes essential in the investigation of new strategies for cancer prevention and cure. Thus, this review presents historical aspects and definitions of immunosurveillance and tumor immunoediting, with emphasis on its importance and applicability, such as on the different methods used in immunotherapy. Keywords: immunocompetence; tumor immunology; immunotherapy; tumor progression; immune syste

Tireoidite linfocítica canina em um Bull terrier

A tireoidite linfocítica é uma enfermidade auto-imune e uma das principais afecções tireoidianas, responsáveis por causar hipotireoidismo primário em cães. O presente trabalho relata o caso de um canino, Bull terrier, macho, de dois anos de idade e histórico de morte súbita durante exercício em esteira. À macroscopia, as alterações relevantes compreenderam congestão e edema pulmonar e endocardiose de mitral. Ao exame microscópico foram verificadas endocardiose, aterosclerose em vasos de diversos órgãos e, na tireóide, constatou-se tireoidite linfocítica. O exame anatomopatológico compreendeu ferramenta decisiva na descrição das alterações e conclusão do diagnóstico, visto que não havia diagnóstico prévio da enfermidade

Fibrossarcoma de ducto biliar em gato

Fibrossarcoma felino é uma neoplasia maligna, localmente invasiva e de tecido conjuntivo fibroso que, em alguns gatos, está associada à vacinação, particularmente a vacinas com adjuvantes. Ocasionalmente, fibrossarcoma aparece naturalmente, não associado à vacina. O presente artigo relata o caso de um felino macho de 10 anos de idade, com um histórico de emagrecimento crônico há alguns meses e aumento do volume abdominal cranial. Através de exames ultrassonográfico e radiográfico, identificou-se uma massa na região hipogástrica e diante do quadro, encaminhou-se o animal à laparotomia exploratória. A neoplasia localizava-se na região do ducto biliar e uma segunda massa solitária foi identificada no lobo caudado do fígado. Houve a remoção cirúrgica dos tumores e a coleta de amostras para exame histopatológico. De acordo com os achados dos exames por imagem, avaliação macroscópica e histopatológica, o diagnóstico foi fibrossarcoma primário de ducto biliar

Randomized controlled trial of early arachidonic acid and docosahexaenoic acid enteral supplementation in very preterm infants

[Objective]: To evaluate changes in blood long-chain polyunsaturated fatty acid (LCPUFA) and oxylipin concentrations in very preterm infants from birth to 36 weeks’ postmenstrual age (WPA) after providing an emulsified arachidonic acid (ARA):docosahexaenoic acid (DHA) supplement at two different concentrations.[Study design]: This prospective, randomized trial assigned infants to receive a supplement (1) 80:40 group (80 mg/kg/day ARA and 40 mg/kg/day DHA, n = 9) or (2) 120:60 group (120 mg/kg/day ARA and 60 mg/kg/day DHA, n = 9). Infants received supplement daily from birth until 36 WPA. At baseline, 21 days of life and 36 WPA, the LCPUFAs were measured in plasma by gas chromatography/mass spectrophotometry. Additionally, LCPUFAs and oxylipins were analyzed in whole blood by ultra-high-performance liquid chromatography-tandem mass spectrometry. Furthermore, a sample of oral mucosa was obtained to analyze single-nucleotide polymorphism located in the FADS1 gene by PCR.[Results]: Gestational age was similar between groups (80:40 = 28+6 [27+3; 30+3] completed weeks+days; 120:60 = 29+6 [27+3; 30+5] completed weeks+days, p = 0.83). At 36 WPA, the change in plasma ARA was significantly different between groups (80:40 group = 0.15 [−0.67; 0.69] %nmol, 120:60 = 1.68 [1.38; 3.16] %nmol, p = 0.031). In whole blood, the levels of ARA-derived oxylipins (5-, 8-, 9-, 11-, 15-HETE and 8,9-EET) and EPA-derived oxylipins (18-HEPE) significantly increase from baseline to 36 WPA in the 120:60 group than the 80:40 group.[Conclusion]: Supplementation at high doses (120:60 mg/kg/day) increased levels of ARA, and EPA- and ARA-derived oxylipins compared to low doses (80:40 mg/kg/day). Differences were detected in EPA metabolites without a significant increase in plasma DHA.This article was supported by the 20th National Grants for Research in Life Sciences 2021/2021 from Ramón Areces Foundation (Spain), the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) networking grant 2021, and Spanish Programs for the generation of Knowledge and Scientific and Technological strengthening of the system and oriented to the challenges of Society (PID2020-119084RB-C21 and PID2020-114821RB-I00 funded by MCIN/AEI/10.13039/501100011033) from the Ministry of Science and Innovation (Spain).Peer reviewe

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file