23 research outputs found
HACIA UNA (POÉTICA DE LA) RELACIÓN TRANSANDINA: DE ARCHIPIÉLAGOS CARIBEÑOS Y ANDINOS O ÉDOUARD GLISSANT VS. JOHN V. MURRA
ORIENTACIONES TRANSANDINAS PARA LOS ESTUDIOS ANDINO
Warisata en el arte,la literatura y la política boliviana. Observaciones acerca del impacto de la Escuela Ayllu en la producción artística boliviana y la nueva legislación educativa del gobierno de Evo Morales
Revisitando el teatro de César Vallejo: La piedra cansada y la reorganización de los procesos productivos
El presente artículo invita a una relectura de la obra teatral La piedra
cansada, de César Vallejo, contextualizándola ante el trasfondo de los
discursos vanguardistas e indigenistas de los años 1930 y siguiendo las
pautas marxistas asumidas por el propio autor. Puesto que la base material
determina la superestructura ideológica y estética que se eleva sobre ella,
la reorganización económica de los procesos productivos representada en
la pieza se reflejará también en la reorganización (o rehumanización) de la
‘nueva poesía’ americana que altera el paradigma de la “deshumanización
del arte nuevo” según Ortega y Gasset, ‘autoctonizando’ e ‘indigenizando’
los discursos estéticos.This article invites to revisit César Vallejo’s play La piedra cansada,
situating it in the context of avant-garde and indigenist discourse of the
1930s and interpreting it from the author’s own Marxist point of view.
Given that the material base determines the ideological and aesthetic
superstructure, the economic reorganization of production processes
represented by the play reflects the reorganization (or re-humanization)
of American “nueva poesía” that modifies Ortega y Gasset’s paradigm of
de-humanized modern arts and leads to a process of vernacularization of
aesthetic discourses
‘El soliloquio de los perros’ oder: Der Hund als Erzähler in den Romanen von Luis Rafael Sánchez und Lucía Puenzo
Mito y mónada: la cosmovisión andina como base de la estética vanguardista de Gamaliel Churata
Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution
Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer
Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors
CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology
Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.
The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies