biostudies-literatureLee MYNIDCR NIH HHSe014067https://www.ebi.ac.uk/biostudies/studies/S-EPMC12863322biostudies-literatureUnknown14(1)<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>After profiling all samples, six distinct spatial niches emeJournal for immunotherapy of cancerSingle-cell spatial transcriptomics uncovers niches that govern response to PD-1/PD-L1 blockade in cutaneous squamous cell carcinoma.PMC12863322R35 DE030054Colevas ADShin JHMartinez Ramirez LDivi VZdravkovic SSherman ARSunwoo JBRahman MLee MYStepanek IfalseSingle-cell spatial transcriptomics uncovers niches that govern response to PD-1/PD-L1 blockade in cutaneous squamous cell carcinoma.<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>After profiling all samples, six distinct spatial niches eme2026-01-01T00:00:00Z2026 Jan2026-07-15T00:52:33.199Z2026-06-27T03:05:39.415ZS-EPMC128633224161739610.1136/jitc-2025-014067