RESUMEN
Perioperative arrests are both uncommon and heterogeneous and have not been described or studied to the same extent as cardiac arrest in the community. These crises are usually witnessed, frequently anticipated, and involve a rescuer physician with knowledge of the patient's comorbidities and coexisting anesthetic or surgically related pathophysiology ultimately leading to better outcomes. This article reviews the most probable causes of intraoperative arrest and their management.
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Paro Cardíaco , Médicos , HumanosAsunto(s)
Investigación Biomédica/métodos , Medicina Basada en la Evidencia/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Proyectos de Investigación , Investigación Biomédica/normas , Medicina Basada en la Evidencia/normas , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Proyectos de Investigación/normasRESUMEN
Despite lack of tumor control in many models, spontaneous T cell priming occurs frequently in response to a growing tumor. However, the innate immune mechanisms that promote natural antitumor T cell responses are undefined. In human metastatic melanoma, there was a correlation between a type I interferon (IFN) transcriptional profile and T cell markers in metastatic tumor tissue. In mice, IFN-ß was produced by CD11c(+) cells after tumor implantation, and tumor-induced T cell priming was defective in mice lacking IFN-α/ßR or Stat1. IFN signaling was required in the hematopoietic compartment at the level of host antigen-presenting cells, and selectively for intratumoral accumulation of CD8α(+) dendritic cells, which were demonstrated to be essential using Batf3(-/-) mice. Thus, host type I IFNs are critical for the innate immune recognition of a growing tumor through signaling on CD8α(+) DCs.
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Linfocitos T CD8-positivos/inmunología , Células Dendríticas/inmunología , Interferón Tipo I/inmunología , Subgrupos Linfocitarios/inmunología , Melanoma/inmunología , Transducción de Señal/inmunología , Animales , Línea Celular Tumoral , Humanos , Inmunidad Innata/inmunología , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/patología , Metástasis Linfática/inmunología , Melanoma/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/inmunologíaRESUMEN
Although recent work has suggested that lymphopenia-induced homeostatic proliferation may improve T cell-mediated tumor rejection, there is little direct evidence isolating homeostatic proliferation as an experimental variable, and the mechanism by which improved antitumor immunity occurs via homeostatic proliferation is poorly understood. An adoptive transfer model was developed in which tumor-specific 2C/RAG2(-/-) TCR transgenic CD8+ T cells were introduced either into the lymphopenic environment of RAG2(-/-) mice or into P14/RAG2(-/-) mice containing an irrelevant CD8+ TCR transgenic population. RAG2(-/-), but not P14/RAG2(-/-) recipients supported homeostatic proliferation of transferred T cells as well as tumor rejection. Despite absence of tumor rejection in P14/RAG2(-/-) recipients, 2C cells did become activated, as reflected by CFSE dilution and CD44 up-regulation. However, these cells showed poor IFN-gamma and IL-2 production upon restimulation, consistent with T cell anergy and similar to the hyporesponsiveness induced by administration of soluble peptide Ag. To determine whether homeostatic proliferation could uncouple T cell anergy, anergic 2C cells were transferred into RAG(-/-) recipients, which resulted in vigorous homeostatic proliferation, recovery of IL-2 production, and acquisition of the ability to reject tumors. Taken together, our data suggest that a major mechanism by which homeostatic proliferation supports tumor rejection is by maintaining and/or re-establishing T cell responsiveness.
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Linfocitos T CD8-positivos/inmunología , Proliferación Celular , Anergia Clonal/inmunología , Homeostasis/inmunología , Linfopenia/inmunología , Neoplasias Experimentales/inmunología , Traslado Adoptivo , Animales , Citocinas/inmunología , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Genes RAG-1 , Ratones , Ratones Transgénicos , Receptores de Antígenos de Linfocitos T/genéticaRESUMEN
ICAM-1 has been described to provide both adhesion and costimulatory functions during T cell activation. In the setting of antitumor immunity, ICAM-1/LFA-1 interactions could be important at the level of T cell priming by APCs in draining lymph nodes as well as for transendothelial migration and tumor cell recognition at the tumor site. To determine the contribution of ICAM-1 to tumor rejection in vivo, we performed adoptive transfer of 2C TCR-transgenic/RAG2(-/-) T cells into TCRalpha(-/-) vs ICAM(-/-)/TCRalpha(-/-) recipient animals. ICAM-1-deficient mice successfully rejected HTR.C tumors expressing Ld recognized by the 2C TCR, albeit with a kinetic delay. Inasmuch as HTR.C tumor cells themselves express ICAM-1, a second model was pursued using B16-F10 melanoma cells that lack ICAM-1 expression. These cells were transduced to express the SIYRYYGL peptide recognized by the 2C TCR in the context of Kb, which is cross-presented by APCs in H-2b mice in vivo. These tumors also grew more slowly but were eventually rejected by the majority of ICAM-1(-/-)/TCRalpha(-/-) recipients. Delayed rejection in ICAM-1(-/-) mice was associated with diminished T cell priming as assessed by ELISPOT. In contrast, T cell penetration into the tumor was comparable in wild-type and ICAM-1(-/-) hosts, and adoptively transferred primed effector 2C cells rejected normally in ICAM-1(-/-) recipients. Our results suggest that ICAM-1 contributes to but is not absolutely required for CD8+ T cell-mediated tumor rejection in vivo and dominantly acts at the level of priming rather than the effector phase of the antitumor immune response.