Fibroblasts Impair Migration and Antitumor Activity of NK-92 Lymphocytes in a Melanoma-on-Chip Model

Adoptive cell therapy in solid tumors, such as melanoma, is impaired, but little is known about the role that the fibroblasts present in the tumor microenvironment could exert. However, the mechanism at play is not well understood, partly due to the lack of relevant pre-clinical models. Three-dimensional culture and microfluidic chips are used to recapitulate the dynamic interactions among different types of cells in the tumor microenvironment in controlled and physiological settings. In this brief report, we propose a reductionist melanoma-on-a-chip model for evaluating the essential role of fibroblasts in the antitumor activity of lymphocytes. To this end, 3D melanoma spheroids were monocultured and co-cultured with human dermal fibroblasts and the NK-92 cell migration towards the tumor compartment was tested in a commercially available microfluidic device. Utilizing confocal microscopy, we observed the different recruitment of NK-92 cells in the presence and absence of fibroblasts. Our results show that fibroblastsâ presence inhibits immune effector recruiting by exploiting a 3D pre-clinical tumor model. ; This research was funded by FCT through project BREAST-IT (PTDC/BTM-ORG/28168/2017) under the Compete2020 program. This work was partially supported by IET A. F. Harvey Engineering Research Award 2018 (ENG The Cancers 2022) and "Associazione Italiana Ricerca sul Cancro (AIRC)" IG-2017 No. 20259 (D.S.). D.C. acknowledges the financial support from FCT (CEECIND/00352/2017 and PTDC/BTM-ORG/28070/2017). The support of EU Framework Programme for Research and Innovation H2020 on FoReCaST (grant agreement No. 668983) is significantly acknowledged.