Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy

Publication Date:
2018-02-03
Publisher:
American Association for the Advancement of Science (AAAS)
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
Chemistry and Pharmacology
Geosciences
Computer Science
Medicine
Natural Sciences in General
Physics
Keywords:
Genetics, Immunology, Medicine, Diseases
Published by:
http://www.aaas.org/
_version_ 1836398776765382656
autor Chowell, D., Morris, L. G. T., Grigg, C. M., Weber, J. K., Samstein, R. M., Makarov, V., Kuo, F., Kendall, S. M., Requena, D., Riaz, N., Greenbaum, B., Carroll, J., Garon, E., Hyman, D. M., Zehir, A., Solit, D., Berger, M., Zhou, R., Rizvi, N. A., Chan, T. A.
beschreibung CD8 + T cell–dependent killing of cancer cells requires efficient presentation of tumor antigens by human leukocyte antigen class I (HLA-I) molecules. However, the extent to which patient-specific HLA-I genotype influences response to anti–programmed cell death protein 1 or anti–cytotoxic T lymphocyte–associated protein 4 is currently unknown. We determined the HLA-I genotype of 1535 advanced cancer patients treated with immune checkpoint blockade (ICB). Maximal heterozygosity at HLA-I loci ("A," "B," and "C") improved overall survival after ICB compared with patients who were homozygous for at least one HLA locus. In two independent melanoma cohorts, patients with the HLA-B44 supertype had extended survival, whereas the HLA-B62 supertype (including HLA-B*15:01) or somatic loss of heterozygosity at HLA-I was associated with poor outcome. Molecular dynamics simulations of HLA-B*15:01 revealed different elements that may impair CD8 + T cell recognition of neoantigens. Our results have important implications for predicting response to ICB and for the design of neoantigen-based therapeutic vaccines.
citation_standardnr 6154433
datenlieferant ipn_articles
feed_id 25
feed_publisher American Association for the Advancement of Science (AAAS)
feed_publisher_url http://www.aaas.org/
insertion_date 2018-02-03
journaleissn 1095-9203
journalissn 0036-8075
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher American Association for the Advancement of Science (AAAS)
quelle Science
relation http://science.sciencemag.org/cgi/content/short/359/6375/582?rss=1
schlagwort Genetics, Immunology, Medicine, Diseases
search_space articles
shingle_author_1 Chowell, D., Morris, L. G. T., Grigg, C. M., Weber, J. K., Samstein, R. M., Makarov, V., Kuo, F., Kendall, S. M., Requena, D., Riaz, N., Greenbaum, B., Carroll, J., Garon, E., Hyman, D. M., Zehir, A., Solit, D., Berger, M., Zhou, R., Rizvi, N. A., Chan, T. A.
shingle_author_2 Chowell, D., Morris, L. G. T., Grigg, C. M., Weber, J. K., Samstein, R. M., Makarov, V., Kuo, F., Kendall, S. M., Requena, D., Riaz, N., Greenbaum, B., Carroll, J., Garon, E., Hyman, D. M., Zehir, A., Solit, D., Berger, M., Zhou, R., Rizvi, N. A., Chan, T. A.
shingle_author_3 Chowell, D., Morris, L. G. T., Grigg, C. M., Weber, J. K., Samstein, R. M., Makarov, V., Kuo, F., Kendall, S. M., Requena, D., Riaz, N., Greenbaum, B., Carroll, J., Garon, E., Hyman, D. M., Zehir, A., Solit, D., Berger, M., Zhou, R., Rizvi, N. A., Chan, T. A.
shingle_author_4 Chowell, D., Morris, L. G. T., Grigg, C. M., Weber, J. K., Samstein, R. M., Makarov, V., Kuo, F., Kendall, S. M., Requena, D., Riaz, N., Greenbaum, B., Carroll, J., Garon, E., Hyman, D. M., Zehir, A., Solit, D., Berger, M., Zhou, R., Rizvi, N. A., Chan, T. A.
shingle_catch_all_1 Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy
Genetics, Immunology, Medicine, Diseases
CD8 + T cell–dependent killing of cancer cells requires efficient presentation of tumor antigens by human leukocyte antigen class I (HLA-I) molecules. However, the extent to which patient-specific HLA-I genotype influences response to anti–programmed cell death protein 1 or anti–cytotoxic T lymphocyte–associated protein 4 is currently unknown. We determined the HLA-I genotype of 1535 advanced cancer patients treated with immune checkpoint blockade (ICB). Maximal heterozygosity at HLA-I loci ("A," "B," and "C") improved overall survival after ICB compared with patients who were homozygous for at least one HLA locus. In two independent melanoma cohorts, patients with the HLA-B44 supertype had extended survival, whereas the HLA-B62 supertype (including HLA-B*15:01) or somatic loss of heterozygosity at HLA-I was associated with poor outcome. Molecular dynamics simulations of HLA-B*15:01 revealed different elements that may impair CD8 + T cell recognition of neoantigens. Our results have important implications for predicting response to ICB and for the design of neoantigen-based therapeutic vaccines.
Chowell, D., Morris, L. G. T., Grigg, C. M., Weber, J. K., Samstein, R. M., Makarov, V., Kuo, F., Kendall, S. M., Requena, D., Riaz, N., Greenbaum, B., Carroll, J., Garon, E., Hyman, D. M., Zehir, A., Solit, D., Berger, M., Zhou, R., Rizvi, N. A., Chan, T. A.
American Association for the Advancement of Science (AAAS)
0036-8075
00368075
1095-9203
10959203
shingle_catch_all_2 Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy
Genetics, Immunology, Medicine, Diseases
CD8 + T cell–dependent killing of cancer cells requires efficient presentation of tumor antigens by human leukocyte antigen class I (HLA-I) molecules. However, the extent to which patient-specific HLA-I genotype influences response to anti–programmed cell death protein 1 or anti–cytotoxic T lymphocyte–associated protein 4 is currently unknown. We determined the HLA-I genotype of 1535 advanced cancer patients treated with immune checkpoint blockade (ICB). Maximal heterozygosity at HLA-I loci ("A," "B," and "C") improved overall survival after ICB compared with patients who were homozygous for at least one HLA locus. In two independent melanoma cohorts, patients with the HLA-B44 supertype had extended survival, whereas the HLA-B62 supertype (including HLA-B*15:01) or somatic loss of heterozygosity at HLA-I was associated with poor outcome. Molecular dynamics simulations of HLA-B*15:01 revealed different elements that may impair CD8 + T cell recognition of neoantigens. Our results have important implications for predicting response to ICB and for the design of neoantigen-based therapeutic vaccines.
Chowell, D., Morris, L. G. T., Grigg, C. M., Weber, J. K., Samstein, R. M., Makarov, V., Kuo, F., Kendall, S. M., Requena, D., Riaz, N., Greenbaum, B., Carroll, J., Garon, E., Hyman, D. M., Zehir, A., Solit, D., Berger, M., Zhou, R., Rizvi, N. A., Chan, T. A.
American Association for the Advancement of Science (AAAS)
0036-8075
00368075
1095-9203
10959203
shingle_catch_all_3 Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy
Genetics, Immunology, Medicine, Diseases
CD8 + T cell–dependent killing of cancer cells requires efficient presentation of tumor antigens by human leukocyte antigen class I (HLA-I) molecules. However, the extent to which patient-specific HLA-I genotype influences response to anti–programmed cell death protein 1 or anti–cytotoxic T lymphocyte–associated protein 4 is currently unknown. We determined the HLA-I genotype of 1535 advanced cancer patients treated with immune checkpoint blockade (ICB). Maximal heterozygosity at HLA-I loci ("A," "B," and "C") improved overall survival after ICB compared with patients who were homozygous for at least one HLA locus. In two independent melanoma cohorts, patients with the HLA-B44 supertype had extended survival, whereas the HLA-B62 supertype (including HLA-B*15:01) or somatic loss of heterozygosity at HLA-I was associated with poor outcome. Molecular dynamics simulations of HLA-B*15:01 revealed different elements that may impair CD8 + T cell recognition of neoantigens. Our results have important implications for predicting response to ICB and for the design of neoantigen-based therapeutic vaccines.
Chowell, D., Morris, L. G. T., Grigg, C. M., Weber, J. K., Samstein, R. M., Makarov, V., Kuo, F., Kendall, S. M., Requena, D., Riaz, N., Greenbaum, B., Carroll, J., Garon, E., Hyman, D. M., Zehir, A., Solit, D., Berger, M., Zhou, R., Rizvi, N. A., Chan, T. A.
American Association for the Advancement of Science (AAAS)
0036-8075
00368075
1095-9203
10959203
shingle_catch_all_4 Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy
Genetics, Immunology, Medicine, Diseases
CD8 + T cell–dependent killing of cancer cells requires efficient presentation of tumor antigens by human leukocyte antigen class I (HLA-I) molecules. However, the extent to which patient-specific HLA-I genotype influences response to anti–programmed cell death protein 1 or anti–cytotoxic T lymphocyte–associated protein 4 is currently unknown. We determined the HLA-I genotype of 1535 advanced cancer patients treated with immune checkpoint blockade (ICB). Maximal heterozygosity at HLA-I loci ("A," "B," and "C") improved overall survival after ICB compared with patients who were homozygous for at least one HLA locus. In two independent melanoma cohorts, patients with the HLA-B44 supertype had extended survival, whereas the HLA-B62 supertype (including HLA-B*15:01) or somatic loss of heterozygosity at HLA-I was associated with poor outcome. Molecular dynamics simulations of HLA-B*15:01 revealed different elements that may impair CD8 + T cell recognition of neoantigens. Our results have important implications for predicting response to ICB and for the design of neoantigen-based therapeutic vaccines.
Chowell, D., Morris, L. G. T., Grigg, C. M., Weber, J. K., Samstein, R. M., Makarov, V., Kuo, F., Kendall, S. M., Requena, D., Riaz, N., Greenbaum, B., Carroll, J., Garon, E., Hyman, D. M., Zehir, A., Solit, D., Berger, M., Zhou, R., Rizvi, N. A., Chan, T. A.
American Association for the Advancement of Science (AAAS)
0036-8075
00368075
1095-9203
10959203
shingle_title_1 Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy
shingle_title_2 Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy
shingle_title_3 Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy
shingle_title_4 Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy
timestamp 2025-06-30T23:32:27.978Z
titel Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy
titel_suche Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy
topic W
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uid ipn_articles_6154433