Aboulkheyr Es et al.3535. H. Aboulkheyr Es, B. Bigdeli, S. Zhand, A. R. Aref, J. P. Thiery, and M. E. Warkiani, J. Cell. Physiol. 236, 3918 (2021). https://doi.org/10.1002/jcp.30135Gene expression profile analysis, including the PD1/PD-L1 geneMCF7Coculturing an epithelial-like/low-expressing PD-L1 breast cancer cell line with MSC-CM3 days3D culture chip (AIM Biotech)Collagen gel solutionThe devices are made up of two parallel communication channels situated on either side of an expanded center area holding gelSehgal et al.3636. K. Sehgal, A. Portell, E. V. Ivanova, P. H. Lizotte, N. R. Mahadevan, J. R. Greene, A. Vajdi, C. Gurjao, T. Teceno, L. J. Taus, T. C. Thai, S. Kitajima, D. Liu, T. Tani, M. Noureddine, C. J. Lau, P. T. Kirschmeier, D. Liu, M. Giannakis, R. W. Jenkins, P. C. Gokhale, S. Goldoni, M. Pinzon-Ortiz, W. D. Hastings, P. S. Hammerman, J. J. Miret, C. P. Paweletz, and D. A. Barbie, J. Clin. Invest. 131, e135038 (2021). https://doi.org/10.1172/JCI135038Bulk RNA-seq analysis of MC38 MDOTS after PD-1 blockadeMC38MC38 MDOTS treated with αPD-1, IgG2a, αCD8a, αIFN-γ, IL-6, TNF-α, and/or LCL161 in gel6 days3D culture chip (AIM Biotech)Collagen gel solutionThree channels per microfluidic chamber: center channel used for gel loading and two side channels used for media3737. R. W. Jenkins, A. R. Aref, P. H. Lizotte, E. Ivanova, S. Stinson, C. W. Zhou, M. Bowden, J. H. Deng, H. Y. Liu, D. N. Miao, M. X. He, W. Walker, G. Zhang, T. Tian, C. R. Cheng, Z. Wei, S. Palakurthi, M. Bittinger, H. Vitzthum, J. W. Kim, A. Merlino, M. Quinn, C. Venkataramani, J. A. Kaplan, A. Portell, P. C. Gokhale, B. Phillips, A. Smart, A. Rotem, R. E. Jones, L. Keogh, M. Anguiano, L. Stapleton, Z. H. Jia, M. Barzily-Rokni, I. Canadas, T. C. Thai, M. R. Hammond, R. Vlahos, E. S. Wang, H. Zhang, S. Li, G. J. Hanna, W. Huang, M. P. Hoang, A. Piris, J. P. Eliane, A. O. Stemmer-Rachamimov, L. Cameron, M. J. Su, P. Shah, B. Izar, M. Thakuria, N. R. LeBoeuf, G. Rabinowits, V. Gunda, S. Parangi, J. M. Cleary, B. C. Miller, S. Kitajima, R. Thummalapalli, B. C. Miao, T. U. Barbie, V. Sivathanu, J. H. Wong, W. G. Richards, R. Bueno, C. H. Yoon, J. Miret, M. Herlyn, L. A. Garraway, E. M. Van Allen, G. J. Freeman, P. T. Kirschmeier, J. H. Lorch, P. A. Ott, F. S. Hodi, K. T. Flaherty, R. D. Kamm, G. M. Boland, K. K. Wong, D. Dornan, C. P. Paweletz, and D. A. Barbie, Cancer Discov. 8, 196 (2018). https://doi.org/10.1158/2159-8290.CD-17-0833,3838. A. R. Aref, M. Campisi, E. Ivanova, A. Portell, D. Larios, B. P. Piel, N. Mathur, C. S. Zhou, R. V. Coakley, A. Bartels, M. Bowden, Z. Herbert, S. Hill, S. Gilhooley, J. Carter, I. Canadas, T. C. Thai, S. Kitajima, V. Chiono, C. P. Paweletz, D. A. Barbie, R. D. Kamm, and R. W. Jenkins, Lab Chip 18, 3129 (2018). https://doi.org/10.1039/C8LC00322JCui et al.3939. X. Cui, C. Ma, V. Vasudevaraja, J. Serrano, J. Tong, Y. Peng, M. Delorenzo, G. Shen, J. Frenster, R.-T. T. Morales, W. Qian, A. Tsirigos, A. S. Chi, R. Jain, S. C. Kurz, E. P. Sulman, D. G. Placantonakis, M. Snuderl, and W. Chen, Elife 9, e52253 (2020).Optimized PD-1 immunotherapyPatient-derived GBM cellsGlioblastoma-on-a-chip2–3 daysSU-8, PDMSMatrigelThe microfluidic device has a vascular-seeding channel, a hydrogel loading channel, and a medium infusion channelAboulkheyr Es et al.2828. H. Aboulkheyr Es, S. Zhand, J. P. Thiery, and M. E. Warkiani, Integr. Biol. 12, 188 (2020). https://doi.org/10.1093/intbio/zyaa014The immune-suppressive potential of PFD therapy in breast cancer cells by treating CAF inside the TMEMCF7Cocultured tumor cells with CAF cells3 days3D culture chip (AIM Biotech)Collagen gel solutionThe devices are made up of two media channels that are situated on each side of a long central section known as the gel channelAnastasiadou et al.4040. E. Anastasiadou, D. Stroopinsky, S. Alimperti, A. L. Jiao, A. R. Pyzer, C. Cippitelli, G. Pepe, M. Severa, J. Rosenblatt, M. P. Etna, S. Rieger, B. Kempkes, E. M. Coccia, S. J. H. Sui, C. S. Chen, S. Uccini, D. Avigan, A. Faggioni, P. Trivedi, and F. J. Slack, Leukemia 33, 132 (2019). https://doi.org/10.1038/s41375-018-0178-xPD-L1 inhibition in immunotherapy and miR-34a dysregulation in cancersU2932, SUDHL5, OMA4, and DG75In vitro 3D biomimetic model2 daysPDMSType 1 collagen, fibronectinA cylindrical channel is formed in a 3D collagen matrix within a microfabricated PDMS gasket4141. S. Alimperti, T. Mirabella, V. Bajaj, W. Polacheck, D. M. Pirone, J. Duffield, J. Eyckmans, R. K. Assoian, and C. S. Chen, Proc. Natl. Acad. Sci. U.S.A. 114, 8758 (2017). https://doi.org/10.1073/pnas.1618333114,4242. D. H.-T. Nguyen, S. C. Stapleton, M. T. Yang, S. S. Cha, C. K. Choi, P. A. Galie, and C. S. Chen, Proc. Natl. Acad. Sci. U.S.A. 110, 6712 (2013). https://doi.org/10.1073/pnas.1221526110Jenkins et al.3737. R. W. Jenkins, A. R. Aref, P. H. Lizotte, E. Ivanova, S. Stinson, C. W. Zhou, M. Bowden, J. H. Deng, H. Y. Liu, D. N. Miao, M. X. He, W. Walker, G. Zhang, T. Tian, C. R. Cheng, Z. Wei, S. Palakurthi, M. Bittinger, H. Vitzthum, J. W. Kim, A. Merlino, M. Quinn, C. Venkataramani, J. A. Kaplan, A. Portell, P. C. Gokhale, B. Phillips, A. Smart, A. Rotem, R. E. Jones, L. Keogh, M. Anguiano, L. Stapleton, Z. H. Jia, M. Barzily-Rokni, I. Canadas, T. C. Thai, M. R. Hammond, R. Vlahos, E. S. Wang, H. Zhang, S. Li, G. J. Hanna, W. Huang, M. P. Hoang, A. Piris, J. P. Eliane, A. O. Stemmer-Rachamimov, L. Cameron, M. J. Su, P. Shah, B. Izar, M. Thakuria, N. R. LeBoeuf, G. Rabinowits, V. Gunda, S. Parangi, J. M. Cleary, B. C. Miller, S. Kitajima, R. Thummalapalli, B. C. Miao, T. U. Barbie, V. Sivathanu, J. H. Wong, W. G. Richards, R. Bueno, C. H. Yoon, J. Miret, M. Herlyn, L. A. Garraway, E. M. Van Allen, G. J. Freeman, P. T. Kirschmeier, J. H. Lorch, P. A. Ott, F. S. Hodi, K. T. Flaherty, R. D. Kamm, G. M. Boland, K. K. Wong, D. Dornan, C. P. Paweletz, and D. A. Barbie, Cancer Discov. 8, 196 (2018). https://doi.org/10.1158/2159-8290.CD-17-0833MDOTS/PDOTS profiling to identify biomarkers associated with a PD-1 blockade response and resistanceMC38 and B16F10MDOTS/PDOTS-on-a-chip3–6 daysPDMS and DAX-1 3D cell culture chip (AIM Biotech)Type 1 collagenThe spheroid-collagen was inserted into the device's center gel chamber, PDOTS/MDOTS-containing collagen hydrogels were hydrated with medium with or without the specified therapeutic monoclonal antibodiesLee et al.4343. J. R. Lee, D. J. B. Bechstein, C. C. Ooi, A. Patel, R. S. Gaster, E. Ng, L. C. Gonzalez, and S. X. Wang, Nat. Commun. 7, 12220 (2016).Characterize the interaction of PD-1/PD-L1 and PD-L2COS-7 cellsNanosensor platform integrated with a microfluidic chip2 daysSU-8N/AThe microfluidic chip includes two structural layers that are joined together by thermal diffusion. Vertical vias link the bottom layer to the top layer, which contains four channels that interact with the magneto-nanosensor chip