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Peripheral blood could offer a minimally invasive and dynamic source for predictive biomarkers of ICI therapy.<\/jats:p>\n                  <jats:p>This study evaluated circulating immune cell frequencies and phenotypes before and during ICI therapy to identify tumor-agnostic blood-based biomarkers. We analyzed routine blood immune cell counts in a retrospective cohort of 202 patients treated with ICIs. Next, we investigated the findings in a prospectively collected cohort of 45 patients using multiparametric flow cytometry for characterization of immune cell subsets. We considered early radiological response, progression-free survival (PFS), and overall survival (OS) as clinical outcomes.<\/jats:p>\n                  <jats:p>\n                    Higher pre-treatment monocyte and lower lymphocyte counts were consistently associated with inferior PFS and OS but not with early radiological response in the retrospective cohort. In the prospective cohort, detailed immunophenotyping identified elevated pre-treatment frequencies of intermediate (CD14\u207aCD16\u207a) monocytes as a marker of poorer PFS and OS. Within lymphocyte subsets, higher T cell frequencies were associated with better OS, and a higher pre-treatment frequency of CD226-expressing CD8\u207a memory T cells with better ICI response. ICI therapy induced increase in TIGIT\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    and CD4\n                    <jats:sup>+<\/jats:sup>\n                    memory T cell subsets, regardless of treatment response.\n                  <\/jats:p>\n                  <jats:p>In conclusion, elevated pre-treatment levels of blood monocytes, together with decreased levels lymphocytes, were associated with poor survival of ICI-treated patients. Although detailed immunophenotyping of pre-treatment blood immune cell populations showed limited predictive utility, specific subpopulations, such as intermediate monocytes and CD226\u207aCD8\u207a memory T cells, may harbor potential as prognostic\/predictive indicators.<\/jats:p>","DOI":"10.1007\/s00262-026-04404-0","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T13:05:26Z","timestamp":1777727126000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of the predictive and prognostic potential of blood immune cell profiles in metastatic cancer patients treated with immune checkpoint inhibitors"],"prefix":"10.1007","volume":"75","author":[{"given":"Veera","family":"Nurmela","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna-Mari","family":"Schroderus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satu","family":"Tiainen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Outi","family":"Kuittinen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olli","family":"Tenhunen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Jokim\u00e4ki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanna","family":"Suoranta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanna","family":"Pasonen-Sepp\u00e4nen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tero","family":"Siev\u00e4nen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuure","family":"Kinnunen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aino","family":"R\u00f6nk\u00e4","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,2]]},"reference":[{"issue":"1","key":"4404_CR1","doi-asserted-by":"publisher","first-page":"3801","DOI":"10.1038\/s41467-020-17670-y","volume":"11","author":"C Robert","year":"2020","unstructured":"Robert C (2020) A decade of immune-checkpoint inhibitors in cancer therapy. 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ST reports personal fees for speaking at symposia, consulting or financial support for attending conferences from Astra Zeneca, BMS, Merck, MSD, Novartis, Pfizer and Roche. None of the financial support was related to the present study. All other authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}],"article-number":"161"}}