The genetic structure and adaptation of Andean highlanders and Amazonians are influenced by the interplay between geography and culture.

Western South America was one of the worldwide cradles of civilization. The well-known Inca Empire was the tip of the iceberg of an evolutionary process that started 11,000 to 14,000 years ago. Genetic data from 18 Peruvian populations reveal the following: 1) The between-population homogenization of the central southern Andes and its differentiation with respect to Amazonian populations of similar latitudes do not extend northward.

Targeting PD-L1 in non-small cell lung cancer using CAR T cells.

Antibodies against programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have dramatically changed the landscape of therapies for non-small cell lung carcinoma (NSCLC); however, the majority of patients do not respond to these agents. In addition, hyperprogressive disease (HPD) develops in a larger portion of NSCLC patients treated with PD-1/PD-L1 inhibitors than in patients treated with standard chemotherapy. The use of chimeric antigen receptor (CAR) T cells has been successful to treat blood cancers but not for solid tumors like NSCLC.

MR1-Restricted T Cells in Cancer Immunotherapy.

Major histocompatibility complex class I-related (MR1) was first identified as a cell membrane protein involved in the development and expansion of a unique set of T cells expressing an invariant T-cell receptor (TCR) α-chain. These cells were initially discovered in mucosal tissues, such as the intestinal mucosa, so they are called mucosal-associated invariant T (MAIT) cells. MR1 senses the presence of intermediate metabolites of riboflavin and folic acid synthesis that have been chemically modified by the side-products of glycolysis, glyoxal or methylglyoxal.

Evolutionary genomic dynamics of Peruvians before, during, and after the Inca Empire.

Native Americans from the Amazon, Andes, and coastal geographic regions of South America have a rich cultural heritage but are genetically understudied, therefore leading to gaps in our knowledge of their genomic architecture and demographic history. In this study, we sequence 150 genomes to high coverage combined with an additional 130 genotype array samples from Native American and mestizo populations in Peru. The majority of our samples possess greater than 90% Native American ancestry, which makes this the most extensive Native American sequencing project to date.

An Isolated TCR αβ Restricted by HLA-A*02:01/CT37 Peptide Redirecting CD8 T Cells To Kill and Secrete IFN-γ in Response to Lung Adenocarcinoma Cell Lines.

Lung cancer is a leading cause of cancer-related death among both men and women in the United States, where non-small cell lung cancer accounts for ∼85% of lung cancer. Lung adenocarcinoma (ADC) is the major histologic subtype. The presence of actionable mutations prompts the use of therapies designed to specifically address the deleterious effects of those cancer-driving mutations; these therapies have already shown promise in cases carrying those actionable mutations (∼30%).

Inverse relationship between TCTP/RhoA and p53 /cyclin A/actin expression in ovarian cancer cells.

The translationally controlled tumor protein (TCTP) plays a role in cell growth, cell cycle and cancer progression. TCTP controls negatively the stability of the p53 tumor suppressor protein and interacts with the cellular cytoskeleton. The deregulation of the actin and cytokeratin cytoskeleton is responsible for the increased migratory activity of tumor cells and is linked with poor patient outcome.

Joint effect of MCP-1 genotype GG and MMP-1 genotype 2G/2G increases the likelihood of developing pulmonary tuberculosis in BCG-vaccinated individuals.

We previously reported that the -2518 MCP-1 genotype GG increases the likelihood of developing tuberculosis (TB) in non-BCG-vaccinated Mexicans and Koreans. Here, we tested the hypothesis that this genotype, alone or together with the -1607 MMP-1 functional polymorphism, increases the likelihood of developing TB in BCG-vaccinated individuals. We conducted population-based case-control studies of BCG-vaccinated individuals in Mexico and Peru that included 193 TB cases and 243 healthy tuberculin-positive controls from Mexico and 701 TB cases and 796 controls from Peru.

Associations of MHC ancestral haplotypes with resistance/susceptibility to AIDS disease development.

We tested the association of MHC ancestral haplotypes with rapid or slow progression to AIDS by comparing their frequencies in the French genetics of resistance/susceptibility to immunodeficiency virus cohort with that reported in a control French population. Seven ancestral haplotypes were identified in the genetics of resistance/susceptibility to immunodeficiency virus cohort with a frequency >1%. The 8.

Linkage disequilibrium between HLA-DPB1 alleles and retinoid X receptor beta haplotypes.

The human retinoid X receptor beta (RXRB) gene maps to the major histocompatibility complex (MHC) region, between KE4 and COL11A2, approximately 130-kb centromeric to HLA-DPB1. We have recently reported a new polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to detect the G to T single nucleotide polymorphism (SNP) located seven nucleotides after the tenth exon of the RXRB gene, or 3'end+7 position according to existing nomenclature. We also reported strong linkage disequilibrium between the HLA-DPB1*0401 and RXRB+7*T alleles.