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In this exploratory study, we aimed to understand the effects of anti-PD1 therapy on the patients\u2019 immune system and discover the characteristics that would result in successful treatment. We collected peripheral blood (PB) samples from 17 immuno-oncology-na\u00efve metastatic melanoma patients before and after 1 and 3\u00a0months of anti-PD1 therapy. In addition, matching tumor biopsies at the time of diagnosis were collected for tissue microarray. The complete blood counts, PB immunophenotype, serum cytokine profiles, and tumor-infiltrating lymphocytes were analyzed and correlated with the clinical data. Patients were categorized based on their disease control into responders (complete response, partial response, stable disease\u2009&gt;\u20096\u00a0months, <jats:italic>N<\/jats:italic>\u2009=\u200911) and non-responders (progressive disease, stable disease\u2009\u2264\u20096\u00a0months, <jats:italic>N<\/jats:italic>\u2009=\u20096). During therapy, the PB natural killer T (NKT) cell frequency, expression of CD25 and CD45RO on cytotoxic natural killer (NK) cells, and serum CXC chemokine levels were significantly increased in responders. Furthermore, higher age together with age-associated characteristics from PB, lower frequency of PB-na\u00efve CD8<jats:sup>+<\/jats:sup> T cells, and elevated levels of serum MCP-4 and OPG were discovered as baseline predictors of treatment response. We therefore propose that in addition to T cells, anti-PD1 treatment is associated with NK- and NKT-cell population dynamics, and that the age-associated characteristics from PB together with older age may contribute to prolonged PFS in anti-PD1-treated melanoma patients.<\/jats:p>","DOI":"10.1007\/s00262-020-02497-9","type":"journal-article","created":{"date-parts":[[2020,2,8]],"date-time":"2020-02-08T10:02:42Z","timestamp":1581156162000},"page":"717-730","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Age-associated changes in the immune system may influence the response to anti-PD1 therapy in metastatic melanoma patients"],"prefix":"10.1007","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0249-3374","authenticated-orcid":false,"given":"Henna","family":"Kasanen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0139-4596","authenticated-orcid":false,"given":"Micaela","family":"Hernberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5720-5993","authenticated-orcid":false,"given":"Siru","family":"M\u00e4kel\u00e4","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Br\u00fcck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Juteau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9888-3635","authenticated-orcid":false,"given":"Laura","family":"Kohtam\u00e4ki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9387-1179","authenticated-orcid":false,"given":"Mette","family":"Ilander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0816-8241","authenticated-orcid":false,"given":"Satu","family":"Mustjoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5587-8844","authenticated-orcid":false,"given":"Anna","family":"Kreutzman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,8]]},"reference":[{"key":"2497_CR1","doi-asserted-by":"crossref","first-page":"9585614","DOI":"10.1155\/2018\/9585614","volume":"2018","author":"J Koury","year":"2018","unstructured":"Koury J, Lucero M, Cato C, Chang L, Geiger J, Henry D, Hernandez J, Hung F, Kaur P, Teskey G, Tran A (2018) Immunotherapies: exploiting the immune system for cancer treatment. 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Clin Cancer Res 24:5347\u20135356","journal-title":"Clin Cancer Res"}],"container-title":["Cancer Immunology, Immunotherapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-020-02497-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00262-020-02497-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-020-02497-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T03:19:58Z","timestamp":1612840798000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00262-020-02497-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,8]]},"references-count":45,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["2497"],"URL":"https:\/\/doi.org\/10.1007\/s00262-020-02497-9","relation":{},"ISSN":["0340-7004","1432-0851"],"issn-type":[{"value":"0340-7004","type":"print"},{"value":"1432-0851","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,8]]},"assertion":[{"value":"20 August 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 February 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"Micaela Hernberg has received honoraria from Pierre Fabre, Novartis, Bristol-Myers Squibb (BMS), Merck Sharp & Dohme (MSD), Roche, Amgen, Sanofi and Incyte. Siru M\u00e4kel\u00e4 has had a paid consulting and advisory role with MSD, BMS, Novartis, Sanofi, Amgen and Roche. Satu Mustjoki has received honoraria and research funding from BMS and research funding from Novartis and Pfizer. The remaining authors declare no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was approved by the Helsinki University Hospital ethical committee (healthy volunteers Dnro 303\/12\/03\/01\/2011 and melanoma patients Dnro 115\/13\/03\/02\/15). The study was conducted in accordance with the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and ethical standards"}},{"value":"All samples involving patients and healthy volunteers were taken after giving a signed informed consent. The patients and healthy volunteers consented to the use of their specimens in terms of data research and publication use.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}