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- HLA class I loss (1)
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T lymphocytes against tumor-specific mutated neoantigens can induce tumor regression. Also, the size of the immunogenic cancer mutanome is supposed to correlate with the clinical efficacy of checkpoint inhibition. Herein, we studied the susceptibility of tumor cell lines from lymph node metastases occurring in a melanoma patient over several years towards blood-derived, neoantigen-specific CD8+ T cells. In contrast to a cell line established during early stage III disease, all cell lines generated at later time points from stage IV metastases exhibited partial or complete loss of HLA class I expression. Whole exome and transcriptome sequencing of the four tumor lines and a germline control were applied to identify expressed somatic single nucleotide substitutions (SNS), insertions and deletions (indels). Candidate peptides encoded by these variants and predicted to bind to the patient’s HLA class I alleles were synthesized and tested for recognition by autologous mixed lymphocyte-tumor cell cultures (MLTCs). Peptides from four mutated proteins, HERPUD1G161S, INSIG1S238F, MMS22LS437F and PRDM10S1050F, were recognized by MLTC responders and MLTC-derived T cell clones restricted by HLA-A*24:02 or HLA-B*15:01. Intracellular peptide processing was verified with transfectants. All four neoantigens could only be targeted on the cell line generated during early stage III disease. HLA loss variants of any kind were uniformly resistant. These findings corroborate that, although neoantigens represent attractive therapeutic targets, they also contribute to the process of cancer immunoediting as a serious limitation to specific T cell immunotherapy.
Clathrates are candidate materials for thermoelectric applications because of a number of unique properties. The clathrate I phases in the Ba-Ni-Ge ternary system allow controlled variation of the charge carrier concentration by adjusting the Ni content. Depending on the Ni content, the physical properties vary from metal-like to insulator-like and show a transition from p-type to n-type conduction. Here we present first results on the characterization of millimeter-sized single crystals grown by the Bridgman technique. Single crystals with a composition of Ba8Ni3.5Ge42.1h0.4 show metallic behavior (dp/dT > 0) albeit with high resistivity at room temperature [p (300 K) = 1 mOhm cm]. The charge carrier concentration at 300 K, as determined from Hall-effect measurements, is 2.3 e-/unit cell. The dimensionless thermoelectric figure of merit estimated at 680 K is ZT ~ 0.2. Keywords Clathrates - thermoelectric material - intermetallic compound - nickel
he family of cubic noncentrosymmetric 3-4-3 compounds has become a fertile ground for the discovery of novel correlated metallic and insulating phases. Here, we report the synthesis of a new heavy fermion compound, Ce3Bi4Ni3. It is an isoelectronic analog of the prototypical Kondo insulator Ce3Bi4Pt3 and of the recently discovered Weyl-Kondo semimetal Ce3Bi4Pd3. In contrast to the volume-preserving Pt-Pd substitution, structural and chemical analyses reveal a positive chemical pressure effect in Ce3Bi4Ni3 relative to its heavier counterparts. Based on the results of electrical resistivity, Hall effect, magnetic susceptibility, and specific heat measurements, we identify an energy gap of 65–70 meV, about eight times larger than that in Ce3Bi4Pt3 and about 45 times larger than that of the Kondo-insulating background hosting the Weyl nodes in Ce3Bi4Pd3. We show that this gap as well as other physical properties do not evolve monotonically with increasing atomic number, i.e., in the sequence Ce3Bi4Ni3−Ce3Bi4Pd3−Ce3Bi4Pt3, but instead with increasing partial electronic density of states of the 𝑑 orbitals at the Fermi energy. This work opens the possibility to investigate the conditions under which topological states develop in this series of strongly correlated 3-4-3 materials.
The family of cubic noncentrosymmetric 3-4-3 compounds has become a fertile ground for the discovery of novel correlated metallic and insulating phases. Here, we report the synthesis of a new heavy fermion compound, Ce3Bi4Ni3. It is an isoelectronic analog of the prototypical Kondo insulator Ce3Bi4Pt3 and of the recently discovered Weyl-Kondo semimetal Ce3Bi4Pd3. In contrast to the volume-preserving Pt-Pd substitution, structural and chemical analyses reveal a positive chemical pressure effect in Ce3Bi4Ni3 relative to its heavier counterparts. Based on the results of electrical resistivity, Hall effect, magnetic susceptibility, and specific heat measurements, we identify an energy gap of 65-70 meV, about eight times larger than that in Ce3Bi4Pt3 and about 45 times larger than that of the Kondo-insulating background hosting the Weyl nodes in Ce3Bi4Pd3. We show that this gap as well as other physical properties do not evolve monotonically with increasing atomic number, i.e., in the sequence Ce3Bi4Ni3-Ce3Bi4Pd3-Ce3Bi4Pt3, but instead with increasing partial electronic density of states of the d orbitals at the Fermi energy. To understand under which condition topological states form in these materials is a topic for future studies.
The family of cubic noncentrosymmetric 3-4-3 compounds has become a fertile ground for the discovery of novel correlated metallic and insulating phases. Here, we report the synthesis of a new heavy fermion compound, Ce3Bi4Ni3. It is an isoelectronic analog of the prototypical Kondo insulator Ce3Bi4Pt3 and of the recently discovered Weyl-Kondo semimetal Ce3Bi4Pd3. In contrast to the volume-preserving Pt-Pd substitution, structural and chemical analyses reveal a positive chemical pressure effect in Ce3Bi4Ni3 relative to its heavier counterparts. Based on the results of electrical resistivity, Hall effect, magnetic susceptibility, and specific heat measurements, we identify an energy gap of 65-70 meV, about 8 times larger than that in Ce3Bi4Pt3 and about 45 times larger than that of the Kondo-insulating background hosting the Weyl nodes in Ce3Bi4Pd3. We show that this gap as well as other physical properties do not evolve monotonically with increasing atomic number, i.e., in the sequence Ce3Bi4Ni3-Ce3Bi4Pd3-Ce3Bi4Pt3, but instead with increasing partial electronic density of states of the d orbitals at the Fermi energy. To understand under which condition topological states form in these materials is a topic for future studies.