PTU-121 Llt1 Is Upregulated In Hepatocellular Carcinoma And Inhibits Nk Cell Cytotoxicity

Kumar, Naveenta; Mróz, Anna; Aletrari, Mina-Olga; Goldin, Robert; Purbhoo, Marco A.

doi:10.1136/gutjnl-2014-307263.195

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“…Although lectin-like transcript 1 (LLT1) is reportedly not expressed in normal liver tissues, it is upregulated in HCC to inhibit the cytotoxicity of NK cells. 172 In addition to dampening the functional activities of NK cells, the hepatic TME also affects the chemotactic phenotype of NK cells, including by downregulating CCR1, CCR5, and CXCR3. 173 Overexpression of CCL5 in cancer cells by adenovirus increases the chemotaxis of NK-92 cells to the tumor site and enhances their anti-tumor activity.…”

Section: Trafficking Of Nk Cells Into Tumorsmentioning

confidence: 99%

Natural killer cell homing and trafficking in tissues and tumors: from biology to application

Ran

Lin

Tian

et al. 2022

Sig Transduct Target Ther

125

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Natural killer (NK) cells, a subgroup of innate lymphoid cells, act as the first line of defense against cancer. Although some evidence shows that NK cells can develop in secondary lymphoid tissues, NK cells develop mainly in the bone marrow (BM) and egress into the blood circulation when they mature. They then migrate to and settle down in peripheral tissues, though some special subsets home back into the BM or secondary lymphoid organs. Owing to its success in allogeneic adoptive transfer for cancer treatment and its “off-the-shelf” potential, NK cell-based immunotherapy is attracting increasing attention in the treatment of various cancers. However, insufficient infiltration of adoptively transferred NK cells limits clinical utility, especially for solid tumors. Expansion of NK cells or engineered chimeric antigen receptor (CAR) NK cells ex vivo prior to adoptive transfer by using various cytokines alters the profiles of chemokine receptors, which affects the infiltration of transferred NK cells into tumor tissue. Several factors control NK cell trafficking and homing, including cell-intrinsic factors (e.g., transcriptional factors), cell-extrinsic factors (e.g., integrins, selectins, chemokines and their corresponding receptors, signals induced by cytokines, sphingosine-1-phosphate (S1P), etc.), and the cellular microenvironment. Here, we summarize the profiles and mechanisms of NK cell homing and trafficking at steady state and during tumor development, aiming to improve NK cell-based cancer immunotherapy.

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Section: Trafficking Of Nk Cells Into Tumorsmentioning

confidence: 99%