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Increasing evidence points to critical roles for tumor-derived extracellular vesicles (EVs) and immunosuppressive myeloid cells as key factors in this process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Immunophenotyping of the tumor-immune microenvironment was performed using ultrasonic aspirate collected during GBM resection by high-dimensional flow cytometry. EVs collected from patient-derived GBM cell lines were used to condition myeloid cells collected from healthy donors to generate immunosuppressive myeloid cells. siRNA was used to knockdown TIGIT and\/or NLRP3 expression prior to EV conditioning. T cell co-culture studies were performed with donor-matched T cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Immune phenotyping of the tumor microenvironment and EV-conditioned myeloid cells revealed similar immunomodulatory protein expression across myeloid cell populations, with particularly elevated TIGIT expression. Knockdown of TIGIT reduced the immunosuppressive polarization of myeloid cells, resulting in improved T cell function. This finding proceeded in an NLRP3-dependent manner, with substantial co-expression of TIGIT and NLRP3 expression prior to knockdown, and concomitant knockdown of NLRP3 abrogating the effect of TIGIT knockdown. TIGIT expression correlated with increased IL-13 expression, and IL-13 blockade unmasked a pro-inflammatory myeloid cell phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TIGIT expression in myeloid cells in the GBM microenvironment is a functional marker of immunosuppressive activity, with TIGIT knockdown reducing IL-13 expression and unmasking the pro-inflammatory activity of NLRP3. This study bolsters our understanding of the immunosuppressive complexities of the GBM microenvironment and supports attenuation of immunosuppressive myeloid cell activity as a strategy to restore immune function in GBM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noag044","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T12:35:28Z","timestamp":1771936528000},"page":"1426-1441","source":"Crossref","is-referenced-by-count":2,"title":["TIGIT expression dictates the immunosuppressive reprogramming of myeloid cells in glioblastoma"],"prefix":"10.1093","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3078-200X","authenticated-orcid":false,"given":"Mohammad","family":"Asad","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery, Albert Einstein College of Medicine\/Montefiore Medical Center , Bronx"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Inocencio","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Albert Einstein College of Medicine\/Montefiore Medical Center , Bronx"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Mitrasinovic","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Albert Einstein College of Medicine\/Montefiore Medical Center , Bronx"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minori","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Albert Einstein College of Medicine\/Montefiore Medical Center , Bronx"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carly E","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Albert Einstein College of Medicine\/Montefiore Medical Center , Bronx"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adilia","family":"Hormigo","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Albert Einstein College of Medicine\/Montefiore Medical Center , Bronx"},{"name":"Department of Oncology and Neurology, Albert Einstein College of Medicine\/Montefiore Einstein Comprehensive Cancer Center , Bronx"},{"name":"Department of Microbiology & Immunology, Albert Einstein College of Medicine\/Montefiore Medical Center , Bronx"},{"name":"Marilyn and Stanley M. 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