Dataset Information

Protection from tumor recurrence following adoptive immunotherapy varies with host conditioning regimen despite initial regression of autochthonous murine brain tumors.

ABSTRACT: Adoptive T cell transfer (ACT) has achieved clinical success in treating established cancer, particularly in combination with lymphodepleting regimens. Our group previously demonstrated that ACT following whole-body irradiation (WBI) promotes high-level T cell accumulation, regression of established brain tumors, and long-term protection from tumor recurrence in a mouse model of SV40 T antigen-induced choroid plexus tumors. Here we asked whether an approach that can promote strong donor T-cell responses in the absence of WBI might also produce this dramatic and durable tumor elimination following ACT. Agonist anti-CD40 antibody can enhance antigen-specific CD8(+) T-cell responses and has shown clinical efficacy as a monotherapy in the setting of cancer. We show that anti-CD40 conditioning promotes rapid accumulation of tumor-specific donor CD8(+) T cells in the brain and regression of autochthonous T antigen-induced choroid plexus tumors, similar to WBI. Despite a significant increase in the lifespan, tumors eventually recurred in anti-CD40-conditioned mice coincident with loss of T-cell persistence from both the brain and lymphoid organs. Depletion of CD8(+) T cells from the peripheral lymphoid organs of WBI-conditioned recipients failed to promote tumor recurrence, but donor cells persisted in the brains long-term in CD8-depleted mice. These results demonstrate that anti-CD40 conditioning effectively enhances ACT-mediated acute elimination of autochthonous tumors, but suggest that mechanisms associated with WBI conditioning, such as the induction of long-lived T cells, may be critical for protection from tumor recurrence.

SUBMITTER: Cozza EM

PROVIDER: S-EPMC4344424 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Protection from tumor recurrence following adoptive immunotherapy varies with host conditioning regimen despite initial regression of autochthonous murine brain tumors.

Cozza Eugene M EM Cooper Timothy K TK Budgeon Lynn R LR Christensen Neil D ND Schell Todd D TD

Cancer immunology, immunotherapy : CII 20141119 3

Adoptive T cell transfer (ACT) has achieved clinical success in treating established cancer, particularly in combination with lymphodepleting regimens. Our group previously demonstrated that ACT following whole-body irradiation (WBI) promotes high-level T cell accumulation, regression of established brain tumors, and long-term protection from tumor recurrence in a mouse model of SV40 T antigen-induced choroid plexus tumors. Here we asked whether an approach that can promote strong donor T-cell r ...[more]

PMID: 25408469

Similar Datasets

Project description:BackgroundAtrial fibrillation (AF) may occur after an acute precipitant and subsequently resolve. Management guidelines for AF in these settings are unclear as the risk of recurrent AF and related morbidity is poorly understood. We examined the relations between acute precipitants of AF and long-term recurrence of AF in a clinical setting.MethodsFrom a multi-institutional longitudinal electronic medical record database, we identified patients with newly diagnosed AF between 2000 and 2014. We developed algorithms to identify acute AF precipitants (surgery, sepsis, pneumonia, pneumothorax, respiratory failure, myocardial infarction, thyrotoxicosis, alcohol, pericarditis, pulmonary embolism, and myocarditis). We assessed risks of AF recurrence in individuals with and without a precipitant and the relations between AF recurrence and heart failure, stroke, and mortality.ResultsAmong 10 723 patients with newly diagnosed AF (67.9±9.9 years, 41% women), 19% had an acute AF precipitant, the most common of which were cardiac surgery (22%), pneumonia (20%), and noncardiothoracic surgery (15%). The cumulative incidence of AF recurrence at 5 years was 41% among individuals with a precipitant compared with 52% in those without a precipitant (adjusted hazard ratio [HR], 0.75 [95% CI, 0.69-0.81]; P<0.001). The lowest risk of recurrence among those with precipitants occurred with postoperative AF (5-year incidence 32% in cardiac surgery and 39% in noncardiothoracic surgery). Regardless of the presence of an initial precipitant, recurrent AF was associated with increased adjusted risks of heart failure (hazard ratio, 2.74 [95% CI, 2.39-3.15]; P<0.001), stroke (hazard ratio, 1.57 [95% CI, 1.30-1.90]; P<0.001), and mortality (hazard ratio, 2.96 [95% CI, 2.70-3.24]; P<0.001).ConclusionsAF after an acute precipitant frequently recurs, although the risk of recurrence is lower than among individuals without an acute precipitant. Recurrence is associated with substantial long-term morbidity and mortality. Future studies should address surveillance and management after newly diagnosed AF in the setting of an acute precipitant.

Project description:Over the last decades, malaria has declined substantially in The Gambia but its transmission has not been interrupted. In order to better target control interventions, it is essential to understand the dynamics of residual transmission. This prospective cohort study was conducted between June 2013 and April 2014 in six pairs of villages across The Gambia. Blood samples were collected monthly during the transmission season (June-December) from all residents aged ?6 months (4,194 individuals) and then in April (dry season). Entomological data were collected monthly throughout the malaria transmission season. Ownership of Long-Lasting Insecticidal Nets was 71.5% (2766/3869). Incidence of malaria infection and clinical disease varied significantly across the country, with the highest values in eastern (1.7/PYAR) than in central (0.2 /PYAR) and western (0.1/PYAR) Gambia. Malaria infection at the beginning of the transmission season was significantly higher in individuals who slept outdoors (HR = 1.51, 95% CI: 1.02-2.23, p = 0.04) and in those who had travelled outside the village (HR = 2.47, 95% CI: 1.83-3.34, p <0.01). Sub-patent infections were more common in older children (HR = 1.35, 95% CI: 1.04-1.6, p <0.01) and adults (HR = 1.53, 95% CI: 1.23-1.89, p<0.01) than in younger children. The risk of clinical malaria was significantly higher in households with at least one infected individual at the beginning of the transmission season (HR = 1.76, p<0.01). Vector parity was significantly higher in the eastern part of the country, both in the south (90.7%, 117/129, p<0.01) and the north bank (81.1%, 227/280, p<0.01), than in the western region (41.2%, 341/826), indicating higher vector survival. There is still significant residual malaria transmission across The Gambia, particularly in the eastern region. Additional interventions able to target vectors escaping Long-Lasting Insecticidal Nets and indoor residual spraying are needed to achieve malaria elimination.

Dataset Information

Protection from tumor recurrence following adoptive immunotherapy varies with host conditioning regimen despite initial regression of autochthonous murine brain tumors.

Publications

Protection from tumor recurrence following adoptive immunotherapy varies with host conditioning regimen despite initial regression of autochthonous murine brain tumors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure