{"doi":"10.1136/jitc-2025-013763","title":"Single-cell and spatial transcriptome profiling identifies the immunosuppressive spatial niche in\n                    <i>KRAS</i>\n                    -mutant colorectal cancer","abstract":"<jats:sec>\n                    <jats:title>Background</jats:title>\n                    <jats:p>\n                      <jats:italic>KRAS</jats:italic>\n                      is one of the most frequently mutated genes in colorectal cancer (CRC) and plays a crucial role in tumorigenesis, progression, immune evasion, and treatment resistance. The pronounced heterogeneity within\n                      <jats:italic>KRAS</jats:italic>\n                      -mutant CRC highlights the urgent need for more precise and personalized therapeutic approaches.\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods</jats:title>\n                    <jats:p>\n                      To investigate this heterogeneity, we employed single-cell RNA sequencing and spatial transcriptomics to comprehensively characterize the tumor microenvironment of\n                      <jats:italic>KRAS</jats:italic>\n                      -mutant CRC. Data preprocessing and clustering were performed using Scanpy. Spatial cell-type deconvolution was conducted via Cell2location, whereas intercellular communication and spatial dependencies were analyzed using CellChat, MISTy, and stLearn.\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results</jats:title>\n                    <jats:p>\n                      Our analyses revealed that\n                      <jats:italic>KRAS</jats:italic>\n                      -mutant tumor epithelial cells recruit Mono_\n                      <jats:italic>S100A8</jats:italic>\n                      monocytes via the MDK_SDC4 signaling axis. Concurrently, surrounding Fib_\n                      <jats:italic>CTHRC1</jats:italic>\n                      fibroblasts secrete collagen, which interacts with integrin receptors on\n                      <jats:italic>KRAS</jats:italic>\n                      -mutant epithelial cells and contributes to the exclusion of lymphocyte infiltration.\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion</jats:title>\n                    <jats:p>\n                      These cellular components collaboratively established an immunosuppressive spatial niche. These findings offer novel theoretical insights and potential targets for the development of immunoregulatory strategies tailored to\n                      <jats:italic>KRAS</jats:italic>\n                      -mutant CRC.\n                    </jats:p>\n                  </jats:sec>","journal":"Journal for ImmunoTherapy of Cancer","year":2025,"id":648027,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":4,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":601615,"name":"Chao Gu","orcid":"0000-0002-0486-8611","position":1,"is_corresponding":false},{"id":1688575,"name":"Xinsheng Miao","orcid":null,"position":2,"is_corresponding":false},{"id":245522,"name":"Hao Zuo","orcid":"0000-0002-8812-7385","position":3,"is_corresponding":false},{"id":483356,"name":"Wei Xu","orcid":"0000-0002-4727-1540","position":4,"is_corresponding":false},{"id":367401,"name":"Yan Zhang","orcid":"0000-0002-6041-4454","position":5,"is_corresponding":false},{"id":941888,"name":"Wei Tang","orcid":"0000-0001-5691-6251","position":6,"is_corresponding":false},{"id":1574994,"name":"Jianhua Zhu","orcid":null,"position":7,"is_corresponding":false},{"id":176657,"name":"Zheng Yuan","orcid":null,"position":8,"is_corresponding":false},{"id":1688577,"name":"Xinhua Gu","orcid":null,"position":9,"is_corresponding":false},{"id":1688578,"name":"Chenyi Zhong","orcid":"0000-0001-9951-8878","position":10,"is_corresponding":false},{"id":1688579,"name":"Yueming Sun","orcid":"0000-0001-8641-1668","position":11,"is_corresponding":false},{"id":1221937,"name":"Jiahui Zhou","orcid":"0009-0008-3354-369X","position":12,"is_corresponding":false},{"id":297976,"name":"Sheng Yang","orcid":"0009-0006-5815-9307","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Single-cell and spatial transcriptome profiling identifies the immunosuppressive spatial niche in\n                    <i>KRAS</i>\n                    -mutant colorectal cancer","abstract":"<jats:sec>\n                    <jats:title>Background</jats:title>\n                    <jats:p>\n                      <jats:italic>KRAS</jats:italic>\n                      is one of the most frequently mutated genes in colorectal cancer (CRC) and plays a crucial role in tumorigenesis, progression, immune evasion, and treatment resistance. The pronounced heterogeneity within\n                      <jats:italic>KRAS</jats:italic>\n                      -mutant CRC highlights the urgent need for more precise and personalized therapeutic approaches.\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods</jats:title>\n                    <jats:p>\n                      To investigate this heterogeneity, we employed single-cell RNA sequencing and spatial transcriptomics to comprehensively characterize the tumor microenvironment of\n                      <jats:italic>KRAS</jats:italic>\n                      -mutant CRC. Data preprocessing and clustering were performed using Scanpy. Spatial cell-type deconvolution was conducted via Cell2location, whereas intercellular communication and spatial dependencies were analyzed using CellChat, MISTy, and stLearn.\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results</jats:title>\n                    <jats:p>\n                      Our analyses revealed that\n                      <jats:italic>KRAS</jats:italic>\n                      -mutant tumor epithelial cells recruit Mono_\n                      <jats:italic>S100A8</jats:italic>\n                      monocytes via the MDK_SDC4 signaling axis. Concurrently, surrounding Fib_\n                      <jats:italic>CTHRC1</jats:italic>\n                      fibroblasts secrete collagen, which interacts with integrin receptors on\n                      <jats:italic>KRAS</jats:italic>\n                      -mutant epithelial cells and contributes to the exclusion of lymphocyte infiltration.\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion</jats:title>\n                    <jats:p>\n                      These cellular components collaboratively established an immunosuppressive spatial niche. These findings offer novel theoretical insights and potential targets for the development of immunoregulatory strategies tailored to\n                      <jats:italic>KRAS</jats:italic>\n                      -mutant CRC.\n                    </jats:p>\n                  </jats:sec>","is_dataset_classified":null,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41475845","pmcid":"PMC12766835","openalex_id":"https://openalex.org/W7117644308","authors":[],"funders":[{"funder_name":"The Gusu Health Talent Programme Research Project","grant_id":"GSWS2023058","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82273406","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82303086","title":null},{"funder_name":"Suzhou Applied Basic Research (Medical and Health) Technology Innovation Project","grant_id":"SYW2024112","title":null}],"total_grants":4,"fwci":1.687,"citation_percentile":0.85317232,"influential_citations":0,"citation_trend":[{"year":2026,"count":4}],"oa_status":"gold","license":"cc-by-nc","oa_locations":[{"url":"https://doi.org/10.1136/jitc-2025-013763","host_type":"journal"},{"url":"https://doi.org/10.1136/jitc-2025-013763","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1136/jitc-2025-013763","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41475845","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12766835/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12766835","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12766835?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Single-cell and spatial transcriptomics","Immune cells in cancer","Bone and Dental Protein Studies","Humans","Colorectal Neoplasms","Proto-Oncogene Proteins p21(ras)","Single-Cell Analysis","Tumor Microenvironment","Gene Expression Profiling","Mutation","Transcriptome"],"mesh_terms":["Humans","Mutation","Colorectal Neoplasms","Proto-Oncogene Proteins p21(ras)","Gene Expression Profiling","Single-Cell Analysis","Tumor Microenvironment","Transcriptome"],"keywords":["Transcriptome","Profiling (computer programming)","Colorectal cancer","Niche","Gene expression profiling","immunosuppression","Tumor Microenvironment - Tme"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Reduced inequalities"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"geo"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T02:09:40.778003Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}