Differences in tumor initiation and progression of melanoma in the BrafCA;Tyr‐CreERT2;Ptenf/f model between male and female mice

Zhai, Yougang; Haresi, Adil J.; Huang, Lee Wen; Lang, Deborah

doi:10.1111/pcmr.12821

Cited by 12 publications

(4 citation statements)

References 10 publications

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“…Rather, adaptive T-cell therapy against patient-validated neoantigens or therapeutic vaccination against conserved antigens will likely be more beneficial in these patients. Notably prior to treatment with ICB, male sex (and less consistently older age) are associated with higher risk of recurrence and death in melanoma and may stand to benefit more from ICB 43 , 44 , thus it is also possible that overall stronger immune surveillance could prove advantageous in the context of ICB despite differences in the quality of neoantigens. Finally, these findings shed light on the role of immune surveillance in cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Strength of immune selection in tumors varies with sex and age

et al. 2020

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Individual MHC genotype constrains the mutational landscape during tumorigenesis. Immune checkpoint inhibition reactivates immunity against tumors that escaped immune surveillance in approximately 30% of cases. Recent studies demonstrated poorer response rates in female and younger patients. Although immune responses differ with sex and age, the role of MHCbased immune selection in this context is unknown. We find that tumors in younger and female individuals accumulate more poorly presented driver mutations than those in older and male patients, despite no differences in MHC genotype. Younger patients show the strongest effects of MHC-based driver mutation selection, with younger females showing compounded effects and nearly twice as much MHC-II based selection. This study presents evidence that strength of immune selection during tumor development varies with sex and age, and may influence the availability of mutant peptides capable of driving effective response to immune checkpoint inhibitor therapy.

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Section: Discussionmentioning

confidence: 99%

Strength of immune selection in tumors varies with sex and age

et al. 2020

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“…The prevalent influences of sex on the disease phenotypes of many mouse lines have been evaluated [8], including several mouse models for cancers [9][10][11]. Although the incidence and clinical course of CLL is strongly different between men and women [1], the sex-related characteristics of the CLL mouse model remain unexplored.…”

Section: Introductionmentioning

confidence: 99%

Meta-Analysis Reveals Significant Sex Differences in Chronic Lymphocytic Leukemia Progression in the Eµ-TCL1 Transgenic Mouse Model

Koch

Reinartz

Saggau

et al. 2020

Cancers

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The Eµ-TCL1 transgenic mouse model represents the most widely and extensively used animal model for chronic lymphocytic leukemia (CLL). In this report, we performed a meta-analysis of leukemia progression in over 300 individual Eµ-TCL1 transgenic mice and discovered a significantly accelerated disease progression in females compared to males. This difference is also reflected in an aggressive CLL mouse model with additional deletion of Tp53 besides the TCL1 transgene. Moreover, after serial adoptive transplantation of murine CLL cells, female recipients also succumbed to CLL earlier than male recipients. This sex-related disparity in the murine models is markedly contradictory to the human CLL condition. Thus, due to our observation we urge both careful consideration in the experimental design and accurate description of the Eµ-TCL1 transgenic cohorts in future studies.

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“…Interestingly, we noticed a sex dimorphism in melanoma tumor progression where BPC- Panx1 +/+ female mice seemed to have a more aggressive disease (Fig.1E, G) than males of the same cohort. Other researchers have noted this outcome in a C57B/6J background, but the origin of this difference has not been clarified yet [45]. It has been speculated that this may be due to the presence of alternative steroid receptors in melanoma cells or technical limitations with tamoxifen (an estrogen receptor modulator) differentially influencing the mouse sexes in this melanoma model [45].…”

Section: Discussionmentioning

confidence: 96%

Global Pannexin 1-deletion increases tumor-infiltrating lymphocytes in the BRAF/Pten mouse melanoma model

Sanchez-Pupo,

Finch,

Johnston

et al. 2023

Preprint

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Immunotherapies for malignant melanoma seek to boost the anti-tumoral response of CD8+ T cells but have a limited patient response rate, in part due to limited tumoral immune cell infiltration. Genetic or pharmacological inhibition of Pannexin 1 (PANX1) channel-forming protein is known to decrease melanoma cell tumorigenic properties in vitro and ex vivo. Here, we crossed Panx1 knockout (Panx1-/-) mice with the inducible melanoma model: BrafCA, PtenloxP, Tyr::CreERT2 (BPC). We found that deleting the Panx1 gene in mice does not reduce BRAF(V600E)/Pten-driven primary tumor formation or improve survival. Notably, BPC-Panx1-/- mice tumors exhibited a significant infiltration of CD4+, CD8+ T lymphocytes, and increased Granzyme B+ cells with no changes in the expression of early T cell activation marker CD69, LAG-3 checkpoint receptor or PD-L1 in tumors when compared to BPC-Panx1+/+ genotype. Our results suggest that although Panx1 deletion does not overturn the aggressive BRAF/Pten-driven melanoma progression, in vivo, it does increase the infiltration of effector immune T cell populations in the tumor microenvironment. We propose that PANX1-targeted therapy could be explored as a strategy to increase tumor-infiltrating lymphocytes to boost anti-tumor immunity.

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Differences in tumor initiation and progression of melanoma in the Braf^CA;Tyr‐CreERT2;Pten^f/f model between male and female mice

Cited by 12 publications

References 10 publications

Strength of immune selection in tumors varies with sex and age

Strength of immune selection in tumors varies with sex and age

Meta-Analysis Reveals Significant Sex Differences in Chronic Lymphocytic Leukemia Progression in the Eµ-TCL1 Transgenic Mouse Model

Global Pannexin 1-deletion increases tumor-infiltrating lymphocytes in the BRAF/Pten mouse melanoma model

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