Single-cell spatial transcriptomics uncovers niches that govern response to PD-1/PD-L1 blockade in cutaneous squamous cell carcinoma.

ABSTRACT:

Background

Neoadjuvant PD-1/PD-L1 blockade yields robust efficacy in advanced cutaneous squamous cell carcinoma (cSCC), yet many patients fail to achieve a complete or major pathologic response. The reasons why some patients experience response but others do not are unclear.

Methods

We profiled cSCC specimens before, after 1 dose, and after 3-4 doses of PD-1/PD-L1 blockade to uncover resistance mechanisms and predict therapeutic response. In total, 27 patients across three cohorts, including two phase II trials, were studied. We created 1.7 mm tissue-core microarrays and performed single-cell spatial transcriptomics, including spatial clustering, gene-set enrichment, and spatial correlation analyses.

Results

After profiling all samples, six distinct spatial niches eme

SUBMITTER: Lee MY 

PROVIDER: S-EPMC12863322 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature