biostudies-literatureAlmgrami RTPostdoctoral Fellowship ProgramMedical Science and Technology Research Project of Henan ProvinceKey Special Project for International Science and Technology Innovation Cooperation between Governments under the National Key R&amp;D ProgramPostdoctoral Fellowship Program (Grade C)National Natural Science Foundation of China-General ProjectKey Special Project for International Science and Technology Innovation Cooperation between Governments under the National Key R&D ProgramNational Natural Science Foundation of China–General ProjectNational Natural Science Foundation of China Joint Fund Key Support Project319https://www.ebi.ac.uk/biostudies/studies/S-EPMC12480184biostudies-literatureUnknown74(10)<h4>Background</h4>Metastatic lung carcinoma poses considerable treatment difficulties. It exhibits cellular characteristics that differ from those of early-stage cancer. Immunotherapy demonstrates enhanced hope for patients with advanced and metastatic lung cancer. Tumor-associated macrophages (TAMs) may be a contributing factor that diminishes the effectiveness of immunotherapy. Secreted phosphoprotein 1 (SPP1)⁺TAMs are considered to possess immunosuppressive characteristics, as their interaction with CD8⁺ T lymphocytes results in the exhaustion of these cells.<h4>Methods</h4>We analyzed single-cell RNA sequencing datasets of lung cancer metastases in order to examine the development of brain metastatic tumors. Furthermore, the cell-cell interactions between SPP1<sCancer immunology, immunotherapy : CIISingle-cell transcriptomic analyses provide insights into SPP1&lt;sup&gt;+&lt;/sup&gt; TAM-mediated immune suppression and CD8&lt;sup&gt;+&lt;/sup&gt; T cell dysfunction in lung cancer.PMC124801842521023111632022YFE0141000GZC20232435U24A2073482272873Liu JZhang TAlmgrami RTZhao QYou MZhang YfalseSingle-cell transcriptomic analyses provide insights into SPP1&lt;sup&gt;+&lt;/sup&gt; TAM-mediated immune suppression and CD8&lt;sup&gt;+&lt;/sup&gt; T cell dysfunction in lung cancer.<h4>Background</h4>Metastatic lung carcinoma poses considerable treatment difficulties. It exhibits cellular characteristics that differ from those of early-stage cancer. Immunotherapy demonstrates enhanced hope for patients with advanced and metastatic lung cancer. Tumor-associated macrophages (TAMs) may be a contributing factor that diminishes the effectiveness of immunotherapy. Secreted phosphoprotein 1 (SPP1)⁺TAMs are considered to possess immunosuppressive characteristics, as their interaction with CD8⁺ T lymphocytes results in the exhaustion of these cells.<h4>Methods</h4>We analyzed single-cell RNA sequencing datasets of lung cancer metastases in order to examine the development of brain metastatic tumors. Furthermore, the cell-cell interactions between SPP1<s2025-01-01T00:00:00Z2025 Sep2026-06-04T12:18:18.793Z2026-05-09T03:08:01.156ZS-EPMC124801844102104310.1007/s00262-025-04180-3