Activated, adherent natural killer (A-NK) cells represent a distinct subpopulation of interleukin (IL)-2-stimulated NK cells, which are selectively endowed with the increased expression of integrins and ability to adhere to solid surfaces, migrate into, infiltrate, and destroy cancerous tissues. The present study defines the phenotype and functions of precursors of A-NK (pre-A-NK) cells in humans. Peripheral blood pre-A-NK cells, in contrast to the rest of NK cells, express a novel epitope of CD56 neuronal cell adhesion molecule, termed ANK-1, and increased cell-surface levels of integrins. Pre-A-NK cells also express low levels of CD56 and CD161, and some express CD162 receptor, do not express CD25 or activation markers, and are effective mediators of NK cytotoxicity. Thus, pre-A-NK cells are generally similar to CD56(dim) NK cells. However, pre-A-NK cells differ from the main NK cell subpopulation by having a lower expression level of CD16 and a lower ability to mediate redirected antibody-dependent, cell-mediated cytotoxicity. More importantly, pre-A-NK cells are preferentially endowed with the ability to rapidly respond to IL-2 by integrin-mediated adherence to endothelial cells, extracellular matrix, and plastic. This early, specific response of pre-A-NK cells to IL-2 is followed by their activation, vigorous proliferation, and differentiation into phenotypically and functionally similar A-NK cells. Pre-A-NK cells represent only approximately 26% of peripheral blood NK cells but encompass the majority of NK cells in normal and cancerous, solid tissues. We conclude that pre-A-NK cells represent a distinct subset of resting, mature NK cells with the characteristics indicative of their ability to migrate and reside in solid tissues.

Cancer therapy resistance and recurrence (CTRR) are the dominant causes of death in cancer patients. Recent studies have indicated that non-coding RNAs (ncRNAs) can not only reverse the resistance to cancer therapy but also are crucial biomarkers for the evaluation and prediction of CTRR. Herein, we developed CTRR-ncRNA, a knowledgebase of CTRR-associated ncRNAs, aiming to provide an accurate and comprehensive resource for research involving the association between CTRR and ncRNAs. Compared to most of the existing cancer databases, CTRR-ncRNA is focused on the clinical characterization of cancers, including cancer subtypes, as well as survival outcomes and responses to personalized therapy of cancer patients. Information pertaining to biomarker ncRNAs has also been documented for the development of personalized CTRR prediction. A user-friendly interface and several functional modules have been incorporated into the database. Based on the preliminary analysis of genotype–phenotype relationships, universal ncRNAs have been found to be potential biomarkers for CTRR. The CTRR-ncRNA is a translation-oriented knowledgebase and it provides a valuable resource for mechanistic investigations and explainable artificial intelligence-based modeling. CTRR-ncRNA is freely available to the public at http://ctrr.bioinf.org.cn/.

Cancer therapy resistance and recurrence (CTRR) are the dominant causes of death in cancer patients. Recent studies have indicated that non-coding RNAs (ncRNAs) can not only reverse the resistance to cancer therapy but also are crucial biomarkers for the evaluation and prediction of CTRR. Herein, we developed CTRR-ncRNA, a knowledgebase of CTRR-associated ncRNAs, aiming to provide an accurate and comprehensive resource for research involving association between CTRR and ncRNAs. Compared to most of the existing cancer databases, CTRR-ncRNA is focused on the clinical characterization of cancers, including cancer subtypes, as well as survival outcomes and response to personalized therapy of cancer patients. Information pertaining to biomarker ncRNAs has also been documented for the development of personalized CTRR prediction. A user-friendly interface and several functional modules have been incorporated into the database. Based on the preliminary analysis of genotype-phenotype relationships, universal ncRNAs have been found to be potential biomarkers for CTRR. The CTRR-ncRNA is a translation-oriented knowledgebase and it provides a valuable resource for mechanistic investigations and explainable artificial intelligence-based modelling. CTRR-ncRNA is freely available to the public at http://ctrr.bioinf.org.cn/.

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