Advances in adoptive T-cell therapy for metastatic melanoma

Das, Aparimita; Ghose, Aruni; Naicker, Kevin; Sanchez, Elisabet; Chargari, Cyrus; Rassy, Elie; Boussios, Stergios

doi:10.1016/j.retram.2023.103404

Cited by 16 publications

(7 citation statements)

References 130 publications

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“…Moreover, elevated levels of fibroblasts in the TME contribute to increased secretion of metalloproteinases, leading to the further shedding of ligands that could otherwise engage with NK cells [ 49 ]. Additionally, tumor‐associated fibroblasts are known to negatively influence NK cells by inhibiting the upregulation of activating receptors induced by cytokines [ 50 ]. Furthermore, immunosuppression of NK cells can be exerted by exosomes derived from melanoma [ 51 ], which were also not considered in the present study.…”

Section: Discussionmentioning

confidence: 99%

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Global pannexin 1 deletion increases tumor‐infiltrating lymphocytes in the BRAF/Pten mouse melanoma model

Sanchez‐Pupo,

Finch,

Johnston

et al. 2024

Molecular Oncology

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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 the 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. However, tumors in BPC‐Panx1−/− mice exhibited a significant increase in the infiltration of CD8+ T lymphocytes, with no changes in the expression of early T‐cell activation marker CD69, lymphocyte activation gene 3 protein (LAG‐3) checkpoint receptor, or programmed cell death ligand‐1 (PD‐L1) in tumors when compared to the 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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Section: Discussionmentioning

confidence: 99%

“…Additional supporting information may be found online in the Supporting Information section at the end of the article. (49,50). RNASeqV2 data (Batch normalized from Illumina HiSeq) is derived from TCGA Pan-Cancer Atlas datasets, processed, and normalized using RSEM.…”

Section: Supporting Informationmentioning

confidence: 99%

Global pannexin 1 deletion increases tumor‐infiltrating lymphocytes in the BRAF/Pten mouse melanoma model

Sanchez‐Pupo,

Finch,

Johnston

et al. 2024

Molecular Oncology

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“…Notably, HIF-1α has been pinpointed as a central facilitator of resistance to anti-PD-(L)1 treatments [48] , and research illuminates its role in reshaping the immune microenvironment, notably by binding and transactivating the IL-9 and NOS2 promoters in helper T cells within melanoma contexts [49] . Myeloid-derived suppressor cells, T regulatory (Treg) cells and tumour-associated macrophages constitute immunosuppressive cells present within the tumour microenvironment, which release reactive oxygen species (ROS) amongst other factors, effectively inhibiting (natural killer) NK cell response [50] . Our analyses discerned multiple HREs within the PARVB promoter region.…”

Section: Discussionmentioning

confidence: 99%

PARVB promotes malignant melanoma progression and is enhanced by hypoxic conditions

Wang,

Wu,

et al. 2024

Translational Oncology

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“…Moreover, elevated levels of fibroblasts in the TME contribute to increased secretion of metalloproteinases, leading to the further shedding of ligands that could otherwise engage with NK cells [49]. Additionally, tumor-associated fibroblasts are known to Sanchez-Pupo 2023 -Manuscript Draft for Molecular Oncology negatively influence NK cells by inhibiting the upregulation of activating receptors induced by cytokines [50]. Furthermore, immunosuppression of NK cells can be exerted by exosomes derived from melanoma [51], which were also not considered in the present study.…”

Section: Discussionmentioning

confidence: 99%

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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Advances in adoptive T-cell therapy for metastatic melanoma

Cited by 16 publications

References 130 publications

Global pannexin 1 deletion increases tumor‐infiltrating lymphocytes in the BRAF/Pten mouse melanoma model

Global pannexin 1 deletion increases tumor‐infiltrating lymphocytes in the BRAF/Pten mouse melanoma model

PARVB promotes malignant melanoma progression and is enhanced by hypoxic conditions

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

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