Patterns of immune-cell infiltration in murine models of melanoma: roles of antigen and tissue site in creating inflamed tumors

Abstract

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Transient activation of tumoral DNA damage tolerance pathway coupled with immune checkpoint blockade exerts durable tumor regression in mouse melanoma

“…The objective of this study was to assess tumor eradication efficacy of a combination treatment that involves ICB regimen coupled with augmentation of tumoral mutation burden. Because the standard B16 mouse melanoma model (Alvarez, 2002; Ya et al, 2015) shows modest CD8 T cell infiltration (Leick et al, 2019; Quezada et al, 2006), has limited capacity for antigen presentation (Agrawal et al, 2004; Homet Moreno et al, 2016; Merritt et al, 2004), and generates fast growing tumors (Kuczynski et al, 2018), we considered the YUMM (Yale University Mouse Melanoma) model (Meeth et al, 2016), which is based on three human‐relevant melanoma driver mutations; the BrafV600E mutation that activates proliferative signaling and two tumor suppressor loss‐of‐function mutations, Pten −/− and Cdkn2a −/− . Compared to B16F10, YUMM1.7 tumors grow slower and permit greater infiltration of T lymphocytes (Homet Moreno et al, 2016; Meeth et al, 2016; Wang et al, 2017).…”

Associations of immune cell homing gene signatures and infiltrates of lymphocyte subsets in human melanomas: discordance with CD163+ myeloid cell infiltrates

“…We previously reported that melanoma metastases can be categorized into 3 Immunotype Groups based on the extent and patterns of immune cell infiltrates [ 5 ]. Quantification of multiple immune cell groups and examples of the three Immunotype Groups in single- and multi-stained melanoma tumors have been previously reported in both human and murine models, with examples illustrated [ 5 , 33 , 34 ]. In each core, intratumoral immune cells were scored as 1 when immune cells (CD45 + ) were absent or sparse (no more than 50 immune cells per 1 mm diameter core); 2 when intratumoral immune cells were present at > 50 CD45 + cells/core, but were limited to perivascular cuffing around intratumoral blood vessels; 3 when immune cells were diffusely present among tumor cells in different areas of the core.…”

The Barrier Molecules Junction Plakoglobin, Filaggrin, and Dystonin Play Roles in Melanoma Growth and Angiogenesis

“…Next, we tested the hypothesis that BM overexpression limits T-cell infiltration into tumor. The B16-F1 cell line and subcutaneous location were selected because these features result in poorly infiltrated tumors, 29,30 which makes this model a good candidate to evaluate whether deletion of both FLG and DST in B16-F1 would increase immune infiltration in vivo. FLG and DST were targeted with sgRNA to delete both genes (sgFLGDST).…”

“…1E and F). The B16-AAD cell line and intraperitoneal location were selected because of their ability to produce heavily infiltrated tumors, 30 making this a promising model to test whether overexpression of JUP or PKP3 will decrease immune infiltration.JUP mRNA expression was increased 78-fold and PKP3 mRNA expression 48-fold, and overexpression was confirmed by immunoblotting (Fig. 1G and H).…”