Radiotherapy and CD40 Activation Separately Augment Immunity to Checkpoint Blockade in Cancer
نویسندگان
چکیده
منابع مشابه
Induction of potent systemic anti-melanoma immunity through intratumoral CD40 activation and checkpoint blockade
Purpose Agonistic CD40 antibodies generate strong tumor specific CD8 T cell response and anti-tumor activity; however systemic anti-CD40 therapy has been associated with cytokine release syndrome and liver toxicity. We studied the anti-melanoma activity and mechanism of action of a recombinant adenovirus expressing a stabilized version of CD40L (rAd.CD40L) by local intratumoral delivery approac...
متن کاملHeterologous Vaccination and Checkpoint Blockade Synergize To Induce Antileukemia Immunity.
Checkpoint blockade-based immunotherapies are effective in cancers with high numbers of nonsynonymous mutations. In contrast, current paradigms suggest that such approaches will be ineffective in cancers with few nonsynonymous mutations. To examine this issue, we made use of a murine model of BCR-ABL(+) B-lineage acute lymphoblastic leukemia. Using a principal component analysis, we found that ...
متن کاملCombination of radiotherapy and vaccination overcomes checkpoint blockade resistance
The majority of cancer patients respond poorly to either vaccine or checkpoint blockade, and even to the combination of both. They are often resistant to high doses of radiation therapy as well. We examined prognostic markers of immune cell infiltration in pancreatic cancer. Patients with low CD8+ T cell infiltration and high PD-L1 expression (CD8+ TloPD-L1hi) experienced poor outcomes. We deve...
متن کاملCombination central tolerance and peripheral checkpoint blockade unleashes antimelanoma immunity.
Blockade of immune checkpoint proteins (e.g., CTLA-4, PD-1) improves overall survival in advanced melanoma; however, therapeutic benefit is limited to only a subset of patients. Because checkpoint blockade acts by "removing the brakes" on effector T cells, the efficacy of checkpoint blockade may be constrained by the limited pool of melanoma-reactive T cells in the periphery. In the thymus, aut...
متن کاملImmune checkpoint blockade in ovarian cancer
Increased numbers of tumour infiltrating T‑cells have long been associated with a better prognosis in ovarian cancer, which has led to the general assumption of a relevant impact of T‑cellular anti-tumour immunity in this disease. As a consequence of this knowledge, a multitude of immunologic therapies has emerged over the past years. Although some reports could evidence a successful induction ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Cancer Research
سال: 2018
ISSN: 0008-5472,1538-7445
DOI: 10.1158/0008-5472.can-17-3821