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Beyond direct tumor ablation, PDT can modulate the tumor microenvironment, enhancing antitumor immunity and sensitizing tumors to combination therapies. Related sublethal regimens, termed photodynamic priming (PDP), aim to exploit these immunomodulatory effects. While deep tumors can be accessed using fiber\u2010optic or endoscopic light delivery, extending PDT or PDP to disseminated metastatic disease would require numerous invasive insertions, limiting clinical practicality. Here, we examine immune cell\u2010mediated light delivery, in which luciferase\u2010expressing immune cells infiltrate tumors and act as internal bioluminescent sources for photodynamic activation. Although this strategy could enable PDT and PDP across widespread lesions without external illumination, it remains unclear whether far\u2010field photon emission from luciferase is sufficient to activate PS, or whether near\u2010field mechanisms such as bioluminescence resonance energy transfer are required. Using luciferase\u2010engineered tumor\u2010associated macrophages and verteporfin, we observed no detectable ROS generation or tumor cell cytotoxicity in\u00a0vitro. Complementary Monte Carlo simulations incorporating tissue scattering and absorption show that achievable photon fluxes are several orders of magnitude below established thresholds for cytotoxic PDT. These findings quantitatively define the limits of far\u2010field bioluminescence and highlight the need for near\u2010field strategies for immune cell mediated PDT and PDP.<\/jats:p>","DOI":"10.1111\/php.70149","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:27:31Z","timestamp":1790141251000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Far\u2010field bioluminescent immune cell\u2013mediated photodynamic therapy is limited by photon flux"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1633-4173","authenticated-orcid":false,"given":"Ji Tae","family":"Park","sequence":"first","affiliation":[{"name":"Department of Physics Northeastern University  Boston Massachusetts USA"},{"name":"Translational Biophotonics Cluster Northeastern University  Boston Massachusetts USA"},{"name":"Center for Theoretical Biological Physics Northeastern University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5789-2073","authenticated-orcid":false,"given":"Sudip","family":"Timilsina","sequence":"additional","affiliation":[{"name":"Department of Physics Northeastern University  Boston Massachusetts USA"},{"name":"Translational Biophotonics Cluster Northeastern University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5239-561X","authenticated-orcid":false,"given":"Rebecca C.","family":"Harman","sequence":"additional","affiliation":[{"name":"Department of Physics Northeastern University  Boston Massachusetts USA"},{"name":"Translational Biophotonics Cluster Northeastern University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4578-9298","authenticated-orcid":false,"given":"Chi\u2010Yong","family":"Eom","sequence":"additional","affiliation":[{"name":"Meinig School of Biomedical Engineering Cornell University  Ithaca New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1284-8517","authenticated-orcid":false,"given":"Jeonghyun","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Physics Northeastern University  Boston Massachusetts USA"},{"name":"Translational Biophotonics Cluster Northeastern University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Fang","sequence":"additional","affiliation":[{"name":"Translational Biophotonics Cluster Northeastern University  Boston Massachusetts USA"},{"name":"Department of Bioengineering Northeastern University  Boston Massachusetts 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