Spatial statistics infer structured immune signatures in primary prostate cancer.

Authors

Ali Amiryousefi, Jeremiah Wala, Jia-Ren Lin, Brian William Labadie, Aishwarya Atmakuri, Zoltan Maliga, Eamon Toye, Kiranj Chaudagar, Madeleine S Torcasso, Shannon Coy, Giuseppe Nicolo Fanelli, Brigette Kobs, Fabio Socciarelli, Andréanne Gagné, Eliezer M Van Allen, Akash Patnaik, Peter Sorger

Published in

Cancer immunology research. Sep 11, 2026. Epub Sep 11, 2026.

Abstract

The spatial arrangement of immune cells in the tumor microenvironment (TME) varies widely, from dispersed to clustered and tumor excluded to infiltrating. Multiplexed spatial profiling is an effective means of characterizing tumor-infiltrating lymphocytes (TILs) and immune complexes such as tertiary lymphoid structures (TLS) in the TME. However, few approaches have been described for objectively parametrizing patterns of immune organization and assessing their association with biological or clinical variables. This makes it difficult to evaluate whether a set of tumors is relatively immunologically cold or hot. Here we describe an intuitive set of statistical tools (available in the R package, tlsR) for characterizing lymphocyte patterns in the TME of solid cancers. We applied tlsR to primary prostate cancer (PCa), which is often described as immunologically 'cold'. Using a cohort of 29 radical prostatectomy specimens stratified into low Gleason-grade (LGG; n=15) and high Gleason-grades (HGG; n =14) we showed that HGG PCa is significantly more infiltrated than LGG PCa with lymphocytes organized into B cell or T cell enriched immune clusters (BICs and TICs). A subset of these ICs had the B and T cell zonation and follicular dendritic cells characteristic of a bona fide TLS. HGGs were also enriched with ICs containing precursor exhausted T cells (Tpex) and proliferating B cells and their tumor compartments harbor granzyme-B+ cytotoxic T cells in contact with cancer cells. Thus, far from being cold, a subset of HGG PCa has features associated with active immune surveillance, a finding with implications for emerging PCa immunotherapies.

PMID:
42726512
Bibliographic data and abstract were imported from PubMed on 12 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.