41 research outputs found

    Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade.

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    The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor-1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair-deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor. These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair-deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers\u27 tissue of origin

    Bilingual childrenā€™s social preferences hinge on accent

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    Past research finds that monolingual and bilingual children prefer native speakers to individuals who speak in unfamiliar foreign languages or accents. Do children in bilingual contexts socially distinguish among familiar languages and accents and, if so, how do their social preferences based on language and accent compare? The current experiments tested whether 5- to 7-year-olds in two bilingual contexts in the United States demonstrate social preferences among the languages and accents that are present in their social environments. We compared children's preferences based on language (i.e., English vs. their other native language) and their preferences based on accent (i.e., English with a native accent vs. English with a non-native [yet familiar] accent). In Experiment 1, children attending a French immersion school demonstrated no preference between English and French speakers but preferred American-accented English to French-accented English. In Experiment 2, bilingual Korean American children demonstrated no preference between English and Korean speakers but preferred American-accented English to Korean-accented English. Across studies, bilingual children's preferences based on accent (i.e., American-accented English over French- or Korean-accented English) were not related to their own language dominance. These results suggest that children from diverse linguistic backgrounds demonstrate social preferences for native-accented speakers. Implications for understanding the potential relation between social reasoning and language acquisition are discussed

    Infantsā€™ inferences about language are social

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    Blackwell Publishing Ltd Core

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    Human cognition is founded, in part, on four systems for representing objects, actions, number, and space. It may be based, as well, on a fifth system for representing social partners. Each system has deep roots in human phylogeny and ontogeny, and it guides and shapes the mental lives of adults. Converging research on human infants, non-human primates, children and adults in diverse cultures can aid both understanding of these systems and attempts to overcome their limits

    The early social significance of shared ritual actions

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    Many rituals are socially stipulated such that engaging in a group's rituals can fundamentally signal membership in that group. Here, we asked whether infants infer information about people's social affiliation based on whether those people perform the same ritualistic action versus different actions. We presented 16-month-old infants with two people who used the same object to achieve the same goal: turning on a light. In a first study, the actions that the actors used to turn on the light had key properties of ritual: they were not causally necessary to reach the overall goal, and there were no features of the situation that required doing the particular actions. We varied whether the two actors performed the same action or performed different actions to turn on the light. Infants expected people who used the same ritualistic action to be more likely to affiliate than people who used different actions. A second study indicated that these results were not due to perceptual similarity: when the differences in the actors' actions were not marked by properties of ritual, but were instead due to situational constraints, infants expected the actors to affiliate. Thus, infants understand the social significance of people engaging in common, potentially ritualistic actions, and expect these actions to provide information about third-party social relationships

    Friends or foes: Infants use shared evaluations to infer othersā€™ social relationships.

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    Predicting othersā€™ affiliative relationships is critical to social cognition, but there is little evidence of how this ability develops. We examined 9-month-old infantsā€™ inferences about third-party affiliation based on shared and opposing evaluations. Infants expected two people who expressed shared evaluations to interact positively, whereas they expected two people who expressed opposing evaluations to interact negatively. A control condition revealed that infantsā€™ expectations could not be due to mere perceptual repetition. Thus, an abstract understanding that third-party affiliation can be based on shared intentions has roots in the first year of life. These findings have implications for understanding humansā€™ earliest representations of the social world
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