{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:14:56Z","timestamp":1787026496349,"version":"build-2736575974"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T00:00:00Z","timestamp":1643587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Immune checkpoint inhibitor-induced sarcoid-like reactions and tertiary lymphoid structures (TLSs) are increasingly recognized but rarely reported in the same patient. We report a patient with lung adenocarcinoma who displayed sarcoid-like reactions in intrathoracic lymph nodes and tertiary lymphoid structures in surgical tumor after neoadjuvant therapy with nivolumab plus ipilimumab. Pathological examination revealed 50% residual tumor cells after treatment, and the CT evaluation of the primary tumor showed a stable disease. The patient experienced a recurrence eight months after surgery. To identify immune correlates of the limited response to immunotherapy, we conducted genomic and transcriptional assays, multiplex immunoassay, and multiplex immunohistochemistry on the pre- and post-immunotherapy tumor, lymph node, and plasma samples.\n                    <jats:italic>TP53<\/jats:italic>\n                    R181C,\n                    <jats:italic>KRAS<\/jats:italic>\n                    G12C and\n                    <jats:italic>SMAD4<\/jats:italic>\n                    R361H were identified as driver mutations of the tumor. In addition to abundant infiltrated lymphocytes, immunotherapy induced high levels of inhibitory components in post-treatment tissue samples, especially the FOXP3\n                    <jats:sup>+<\/jats:sup>\n                    regulatory T cells in tumor and PD-L1 expression in the lymph node. Despite abundant TLSs in the post-treatment tumor, most TLSs were immature. Moreover, increasing levels of circulating checkpoint proteins BTLA, TIM-3, LAG-3, PD-1, PD-L1, and CTLA4 were observed during immunotherapy. Collectively, our observations revealed that high levels of immunosuppressive molecules in tumor, lymph nodes and\/or in peripheral blood might indicate poor outcomes after immunotherapy, even in the setting of a patient with concurrent sarcoid-like reactions and tertiary lymphoid structures.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2022.794217","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T00:46:35Z","timestamp":1643589995000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Case Report: Sarcoid-Like Reactions and Tertiary Lymphoid Structures Following Dual Checkpoint Inhibition in a Patient with Early-Stage Lung Adenocarcinoma"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiaoliang","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leina","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henghui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changli","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2018.04.031","article-title":"Sarcoidosis-Like 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