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. 2023 Jun 8;11(6):e006749. doi: 10.1136/jitc-2023-006749

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© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.

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Combination of VAX014 with systemic αCTLA-4 in the bilateral intradermal B16F10 model leads to upregulation of multiple immune pathways in distal non-injected tumors. (A) Complete comparative heat maps of immunotranscriptomes from total RNA extracted from distal non-injected B16F10 tumors after weekly intratumoral treatment of the contralateral B16F10 tumor designated for injection with VAX014 as monotherapy versus VAX014/αCTLA combination (n=3/group). Immunotranscriptome analysis was performed on total RNA isolated from non-injected tumors 2 days following the second weekly intratumoral treatment of the contralateral injected tumor with VAX014. (B) Hierarchical list of fold change in individual gene transcripts among select innate and adaptive immune pathway gene networks in non-injected B16F10 tumors from the VAX014/αCTLA-4 combination treatment group versus VAX014 as monotherapy. Red arrow highlights PD-1 gene (Pdcd1) in the T cell function gene network. (C) Comprehensive cytotoxic cell gene network signatures of non-injected B16F10 tumors following intratumoral treatment of the contralateral injected B16F10 tumor with saline, VAX014 monotherapy, systemic αCTLA-4 monotherapy, or VAX014/αCTLA-4 combination (n=3/group). Bar graph represents median values, and statistical significance of cytotoxic cell log abundance was analyzed using Student’s t-test. AG, antigen; DC, dendritic cell; IFN, interferon; log2 FC, log2 fold change; ns, not significant; TNF, tumor necrosis factor.