Publications by authors named "H Halse"
Article Synopsis
- Recent clinical trials of new immune checkpoint protein-targeted antibodies failed to show significant results, primarily because patients weren't screened for target expression prior to treatment.* -
- The study utilized advanced methods like flow cytometry and single-cell RNA sequencing to analyze immune checkpoint expression on T-cells from various primary tumors, revealing extensive variability among patients.* -
- Results indicated that while CD4FoxP3 T-cells co-expressed both stimulatory and inhibitory checkpoints, the expression levels in CD8 T-cells were generally lower, suggesting a need for better-targeted therapies in future cancer immunotherapy trials.*
Immunotherapies have significantly improved the survival of patients in many cancers over the last decade. However, primary and secondary resistances are encountered in most patients. Unravelling resistance mechanisms to cancer immunotherapies is an area of active investigation.
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- - Targeting immune checkpoints like PD1 has improved survival for some cancer patients but many still experience relapse or do not respond to treatments.
- - Neuropilin-1 (NRP1) is identified as a potential immune checkpoint co-receptor that influences CD8 T cell activity in fighting tumors.
- - Research indicates that NRP1 enhances PD-1 activity and is linked to poorer outcomes in patients with metastatic melanoma treated with anti-PD1 therapies, suggesting it could be a target to improve treatment effectiveness.
Background: We aimed to determine the safety and efficacy of nintedanib, an oral anti-angiogenic tyrosine kinase inhibitor, in combination with pembrolizumab, an anti-PD1 immunotherapy, in patients with advanced solid tumors (PEMBIB trial; NCT02856425).
Methods: In this monocentric phase Ib dose escalation cohort, we evaluated escalating doses of nintedanib (Dose level 1 (DL1) = 150 mg bid [bis in die, as twice a day]; DL2 = 200 mg bid, oral delivery) in combination with pembrolizumab (200 mg Q3W, IV). Patients received a 1-week lead-in dose of nintedanib monotherapy prior starting pembrolizumab.
Accumulation of CD103CD8 resident memory T (T) cells in human lung tumors has been associated with a favorable prognosis. However, the contribution of T to anti-tumor immunity and to the response to immune checkpoint blockade has not been clearly established. Using quantitative multiplex immunofluorescence on cohorts of non-small cell lung cancer patients treated with anti-PD-(L)1, we show that an increased density of CD103CD8 lymphocytes in immunotherapy-naive tumors is associated with greatly improved outcomes.
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