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Article History

Received: 10 September 2025

Accepted: 31 January 2026

First Online: 24 February 2026

Declarations

:

: Written and informed consent was obtained from all participants. The study protocol followed the principles of the Declaration of Helsinki and was granted by the La Paz University Hospital Ethics Committee (HULP-PI-1958). Prior to enrolment, all participants were informed about the purpose and procedures of the study and provided written informed consent. To guarantee the confidentiality of the patient data, the information was anonymised. All procedures undertaken as part of the study were in accordance with the relevant national and institutional ethical guidelines.

: All authors have given their approval for the publication of this final version of the manuscript.

: The present study is limited by its small sample size ( n  = 16), which may restrict statistical power and increases the risk of false discoveries when analysing a high-dimensional dataset comprising over 900 immune features. Likewise, the number of individuals suffering from metastases, as well as of survival events, might be inadequate to support robust multivariable survival modelling, and results from these analyses should be interpreted with caution. Moreover, although efforts were made to minimise technical variability through consistent sample processing and acquisition, batch effects cannot be entirely excluded. In view of these considerations, the identified immune alterations should be regarded as hypothesis-generating and require validation in larger independent cohorts to confirm their reproducibility and clinical relevance. Furthermore, complementary functional studies, encompassing cytokine production assays, assessment of immune cell cytotoxicity, and the analysis of checkpoint modulation, will be necessary to elucidate the biological significance of the observed phenotypic associations.

: The authors declare no competing interests.