NK Cell and Fibroblast-Mediated Regulation of Skin Squamous Cell Carcinoma Invasion by CLEC2A Is Compromised in Xeroderma Pigmentosum

Gonçalves-Maia, Maria; Gache, Yannick; Basante, Miguel; Cosson, Estelle; Salavagione, Emie; Muller, M; Bernerd, Françoise; Avril, Marie Françoise; Schaub, Sébastien; Sarasin, Alain; Braud, Véronique M.; Magnaldo, Thierry

doi:10.1016/j.jid.2020.01.021

Cited by 20 publications

(13 citation statements)

References 41 publications

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“…As shown in Figure 1 D, TGF-β, TNF-α, and IFN-γ were the most significantly activated upstream regulators in lesions compared to the surrounding skin. These cytokines have been associated with protumorigenic phenotypes [ 9 , 27 , 28 , 29 ], suggesting that the cSCC microenvironment favors the tumor-promoting TAN phenotype. Consistent with this observation, the analysis of the canonical pathways enriched and modulated in at least one of the three contrasts revealed that CXCL-8 (IL-8) signaling was the most significantly activated pathway ( Figure S2A ).…”

Section: Resultsmentioning

confidence: 99%

Tumor-Associated Neutrophils Dampen Adaptive Immunity and Promote Cutaneous Squamous Cell Carcinoma Development

Khou

Popa

Luci

et al. 2020

Cancers

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Cutaneous squamous cell carcinoma (cSCC) development has been linked to immune dysfunctions but the mechanisms are still unclear. Here, we report a progressive infiltration of tumor-associated neutrophils (TANs) in precancerous and established cSCC lesions from chemically induced skin carcinogenesis. Comparative in-depth gene expression analyses identified a predominant protumor gene expression signature of TANs in lesions compared to their respective surrounding skin. In addition, in vivo depletion of neutrophils delayed tumor growth and significantly increased the frequency of proliferating IFN-γ (interferon-γ)-producing CD8+ T cells. Mechanisms that limited antitumor responses involved high arginase activity, production of reactive oxygen species (ROS) and nitrite (NO), and the expression of programmed death-ligand 1 (PD-L1) on TAN, concomitantly with an induction of PD-1 on CD8+ T cells, which correlated with tumor size. Our data highlight the relevance of targeting neutrophils and PD-L1-PD-1 (programmed death-1) interaction in the treatment of cSCC.

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Section: Resultsmentioning

confidence: 99%

Tumor-Associated Neutrophils Dampen Adaptive Immunity and Promote Cutaneous Squamous Cell Carcinoma Development

Khou

Popa

Luci

et al. 2020

Cancers

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“…Thus, the 802 DEGs were subjected to GO and KEGG pathway analysis. Most genes, such as CCL25, CLEC2A, NLRP4, CTNNA2, CALCA, and KCNE1B were reported participating in tumor microenvironment modulating 15 , 16 , 17 , 18 . Consistently, GO term also revealed that these genes were interacted with immune cells in remodeling immune microenvironment of colon cancer: Antimicrobial humoral response (GO: 0019730), humoral immune response (GO: 0006959), cell killing (GO: 0001906).…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Tumor-Microenvironment-Regulating Factor That Facilitates Tumor Immune Infiltration in Colon Cancer

Wang

et al. 2020

Molecular Therapy - Nucleic Acids

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Colon cancer is one of the most common malignancies causing death worldwide. It is well known that the cells of the tumor microenvironment contribute to the progression and prognosis of colon cancer. However, the gene alterations and potential remodeling mechanisms in the tumor microenvironment of colon cancer remain largely unknown. In this study, immune scores from the ESTIMATE algorithm were used to discriminate between patients with high or low immune-cell infiltration. There were 42 immune differentially expressed genes (DEGs) of prognostic value identified in this study. Among them, KCNJ5 is a key factor in promoting M2 macrophage recruitment and tumor immune infiltration in colon cancer. These findings may provide novel insights for decoding the complicated interplay between cancer cells and the tumor microenvironment as well as for developing new avenues for therapeutic intervention in colon cancer.

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“…Table 1. Known activating and inhibitory receptors and ligands in NK cells in mice and humans [9][10][11]13,14,23,[25][26][27][28][29][30][31][32]. KIRs have a particular nomenclature: the first number following KIR indicates the number of immunoglobulin (Ig)-domains on the extracellular portion of the receptor, the second number indicates the length of the cytoplasmic tail and its activation state [19].…”

Section: Nk Cell Function and Activity In Normal Biology And Malignanciesmentioning

confidence: 99%

Understanding and Targeting Natural Killer Cell-Cancer-Associated Fibroblast Interactions in Pancreatic Ductal Adenocarcinoma

Malchiodi

Weiner

2021

Cancers

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Interactions between natural killer (NK) cells and cancer-associated fibroblasts (CAFs) comprise a relevant but relatively understudied crosstalk relationship within the tumor microenvironment (TME). This review discusses the relevance of both natural killer cell and cancer-associated fibroblast function and activity in cancers, with an emphasis on pancreatic ductal adenocarcinoma (PDAC), incorporating additional insights from other malignancies to inform future directions for research. We describe what is currently known about NK cell-CAF crosstalk and their molecular interactions, how it is possible to exploit NK cell cytotoxicity in tumors and how to target CAFs to enhance efficacy of cancer therapies and cytotoxic immune cells. Although not previously tested in combination, there is an abundance of evidence demonstrating that targeting tumor-promoting CAFs and exploiting NK cells, separately, are beneficial as therapeutic strategies. This raises the possibility that a novel combination regimen addressing these two cell targets may be even more beneficial to eradicate PDAC and other solid tumors.

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NK Cell and Fibroblast-Mediated Regulation of Skin Squamous Cell Carcinoma Invasion by CLEC2A Is Compromised in Xeroderma Pigmentosum

Cited by 20 publications

References 41 publications

Tumor-Associated Neutrophils Dampen Adaptive Immunity and Promote Cutaneous Squamous Cell Carcinoma Development

Tumor-Associated Neutrophils Dampen Adaptive Immunity and Promote Cutaneous Squamous Cell Carcinoma Development

Identification of Novel Tumor-Microenvironment-Regulating Factor That Facilitates Tumor Immune Infiltration in Colon Cancer

Understanding and Targeting Natural Killer Cell-Cancer-Associated Fibroblast Interactions in Pancreatic Ductal Adenocarcinoma

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