2001
DOI: 10.1073/pnas.191371898
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CD40 stimulation accelerates deletion of tumor-specific CD8+T cells in the absence of tumor-antigen vaccination

Abstract: Previous work has established a role for CD40-mediated signals in eliciting helper-dependent CD8 ؉ T cell responses. Here we investigated the effects of in vivo CD40 stimulation on the survival and function of tumor-specific CD8 ؉ T cells in a mouse melanoma model system. We found that agonistic anti-CD40 antibody treatment alone of tumor-bearing mice accelerated the deletion of tumorantigen-specific T cells. However, long-term survival and function of tumor-antigen-specific T cells could be achieved when vira… Show more

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Cited by 78 publications
(65 citation statements)
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“…Instead, we have clearly shown that the administration of agonistic anti-4-1BB mAb initially increases T cell activation and then promotes the clearance of these activated CD4 ϩ T cells, which results in the attenuation of their effector functions. In support of this dual role of a costimulatory molecule, a recently published study showed that the use of agonistic anti-CD40 Ab initially increased the number of tumor-specific CD8 ϩ T cells, and then it accelerated their deletion in a tumor model system (37). In addition, another group has reported that agonistic mAbs against CD40 can successfully control chronic autoimmune inflammatory processes (38).…”
Section: Discussionmentioning
confidence: 97%
“…Instead, we have clearly shown that the administration of agonistic anti-4-1BB mAb initially increases T cell activation and then promotes the clearance of these activated CD4 ϩ T cells, which results in the attenuation of their effector functions. In support of this dual role of a costimulatory molecule, a recently published study showed that the use of agonistic anti-CD40 Ab initially increased the number of tumor-specific CD8 ϩ T cells, and then it accelerated their deletion in a tumor model system (37). In addition, another group has reported that agonistic mAbs against CD40 can successfully control chronic autoimmune inflammatory processes (38).…”
Section: Discussionmentioning
confidence: 97%
“…Recently, it has been reported that CD40 stimulation has an adverse effect on CTL immunity in tumor-bearing mice (26). Although the reasons for this observation are not known, it could be that the timing of anti-CD40 treatment is an important parameter influencing the outcome of treatment.…”
Section: Discussionmentioning
confidence: 99%
“…The role of the antigen in controlling the T cell response to tumors is also unclear. Many studies use transplantable tumors transfected with model antigens so that either transferred T cells or endogenous responses can be monitored [15,16]. Although the endogenous T cell responses to TAAs are typically weak and less amenable to experimentation [17] tumor model systems that employ the endogenous T cell repertoire and natural TAAs may provide more relevant results to guide the design of tumor immunotherapies.…”
Section: Introductionmentioning
confidence: 99%