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

Abstract

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.

Prognostic Significance of Cuproptosis-Related Gene Signatures in Breast Cancer Based on Transcriptomic Data Analysis

“…Here, our study revealed that breast cancer patients in the high-risk group generally showed higher immune infiltration and greater enrichment of immune-related pathways than their counterparts in the low-risk group, indicating that the CRGs risk score model can distinguish the degree of immune infiltration in patients, and cancer-associated inflammation may play important roles in patient prognoses [ 44 ]. Of note, our data also suggested that NK cell activation may help to stratify subpopulation of patients, which makes it a promising new target for tumor immunotherapy [ 45 ]. Additionally, the comparison regarding immune escape between the high- and low-risk subgroups revealed that the high-risk group was associated with a higher potential for immune escape.…”

Chasing Uterine Cancer with NK Cell-Based Immunotherapies

“…dNK cells comprise about 70% of all feto-maternal interface lymphocytes during first-trimester pregnancy in humans, and they support trophoblast invasion and angiogenesis [82][83][84][85]. dNK cells in the uterus highly express CXCR3, with relatively low expression of CXCR4 [32]. Very low CXCR1, CXCR2, CX3CR1, or CCR1, 2, 3 expression has also been observed in dNK cells.…”

Leveraging Natural Killer Cell Innate Immunity against Hematologic Malignancies: From Stem Cell Transplant to Adoptive Transfer and Beyond

“…NK cells are characterized as CD3 − CD56 + large granular lymphocytes consisting of two broad subtypes: the naïve CD56 bright CD16 dim subsets and the more common and mature CD56 dim CD16 + subsets [8]. These cells are broadly distributed across the peripheral blood as well as the bone marrow, lymph nodes, spleen, and liver [9,10]. They partake in several critical roles in the human innate immune system, including surveillance and cytotoxic functions against tumor cells [1].…”