| 1. |
- Donia, Marco, et al.
(författare)
-
Acquired immune resistance follows complete tumor regression without loss of target antigens or IFNγ signaling
- 2017
-
Ingår i: Cancer Research. - 0008-5472. ; 77:17, s. 4562-4566
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer immunotherapy can result in durable tumor regressions in some patients. However, patients who initially respond often experience tumor progression. Here, we report mechanistic evidence of tumoral immune escape in an exemplary clinical case: a patient with metastatic melanoma who developed disease recurrence following an initial, unequivocal radiologic complete regression after T-cell–based immunotherapy. Functional cytotoxic T-cell responses, including responses to one mutant neoantigen, were amplified effectively with therapy and generated durable immunologic memory. However, these immune responses, including apparently effective surveillance of the tumor mutanome, did not prevent recurrence. Alterations of the MHC class I antigen-processing and presentation machinery (APM) in resistant cancer cells, but not antigen loss or impaired IFNγ signaling, led to impaired recognition by tumor-specific CD8þ T cells. Our results suggest that future immunotherapy combinations should take into account targeting cancer cells with intact and impaired MHC class I–related APM. Loss of target antigens or impaired IFNγ signaling does not appear to be mandatory for tumor relapse after a complete radiologic regression. Personalized studies to uncover mechanisms leading to disease recurrence within each individual patient are warranted.
|
|
| 2. |
- Fedorova, I., et al.
(författare)
-
On the non-equilibrium segregation of Boron in 9-12%Cr steels
- 2017
-
Ingår i: 4th International ECCC Creep & Fracture Conference.
-
Konferensbidrag (refereegranskat)abstract
- The addition of only 20-150 ppm of boron to martensitic 9-12%Cr steels has a strong enhancing effect on their creep strength, and boron-added martensitic creep strength enhanced steels have been introduced in power plant constructions. Boron is found to redistribute in the martensitic steels during cooling after normalizing in a non-equilibrium segregation process. In this work we attempt to quantify boron segregation during solution treatment in a martensitic 9%Cr steel containing 108 ppm of boron by atom probe tomography and transmission electron microscopy. The investigated material was a solution treated at 1100C for 1 h and cooled in air. Plate-like boride of Cr2B was found on a prior austenite grain boundary (PAGB). The distribution of B, Cr, Fe, Co, Mo, C and other elements in boride and matrix was quantified. Boron is considered to segregate onto PAGBs by non-equilibrium mechanism.
|
|
