{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:21:46Z","timestamp":1787664106186,"version":"build-2736575974"},"reference-count":232,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82573713, 81802815"],"award-info":[{"award-number":["82573713, 81802815"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007847","name":"Natural Science Foundation of Jilin Province","doi-asserted-by":"publisher","award":["YDZJ202301ZYTS003, YDZJ202501ZYTS114"],"award-info":[{"award-number":["YDZJ202301ZYTS003, YDZJ202501ZYTS114"]}],"id":[{"id":"10.13039\/100007847","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The regulatory role of the nervous system in malignant tumor pathogenesis has emerged as an active and rapidly evolving field in tumor immunology. Within the tumor microenvironment (TME), innervation by the peripheral nervous system has been implicated not only in tumor initiation and progression but also in the establishment of an immunosuppressive network, partly through the reactivation of nerve-dependent developmental and regenerative programs. Although neural signals have been reported to promote immune cell exhaustion, the mechanisms by which they may directly influence the physical properties and biomechanical behavior of immune cells remain largely unexplored. In this review, we propose a testable hypothesis that neurotransmitters within the TME may engage receptors on immune cells and modulate the activity of the dedicator of cytokinesis (DOCK) family of atypical guanine nucleotide exchange factors (GEFs). This putative signaling axis could, in turn, disrupt DOCK-mediated actin cytoskeletal dynamics downstream of Rac\/Cdc42, potentially contributing to cytoskeletal dysfunction, including impaired dendritic cell and macrophage chemotaxis through dense tumor stroma, and defective cytotoxic T-cell immune synapse formation. We synthesize current evidence supporting this framework, highlight critical mechanistic gaps, and outline an evidence map to guide future investigation. We also discuss the translational implications of targeting the proposed neural receptor-DOCK-cytoskeleton axis, while emphasizing that such applications remain speculative and require substantial experimental validation before any clinical translation can be justified.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1927701","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:49:49Z","timestamp":1787662189000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A hypothesis and evidence map for neuroimmune regulation of DOCK-family cytoskeletal programs in solid tumors"],"prefix":"10.3389","volume":"17","author":[{"given":"Lei","family":"Zhou","sequence":"first","affiliation":[{"name":"Cancer Center, First Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuning","family":"Ren","sequence":"additional","affiliation":[{"name":"Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, First Hospital of Jilin University","place":["Changchun, China"]},{"name":"National-Local Joint Engineering Laboratory of Animal Models for Human Disease, First Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Affiliated Hospital of Changchun University of Chinese Medicine","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, First Hospital of Jilin University","place":["Changchun, 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