Dissecting the NK Cell Population in Hematological Cancers Confirms the Presence of Tumor Cells and Their Impact on NK Population Homeostasis

Abstract

The innate immune lymphocyte lineage natural killer (NK) cell protects against multiple pathogens and tumor cells and contains multiple subsets that could have specific activity against different attacks. The presence of viral-sculpted NK populations has already been described, but the presence of cancer-sculpted NK is unknown. Cancer induces a broad NK cell dysfunction, but this is not related to a specific population. Here we investigate NK cell population by Uniform Manifold Approximation and Projection (UMAP) embed maps in Hodgkin lymphoma (HL) and acute myeloid leukemia (AML) patients at diagnosis and, at least 30 days, after treatment, which correlates with tumor cell clearance. Whereas we identified that the NK lineage largely responded to tumor presence by generating antitumor NK cells and renewing NK cell population with immature subsets, we failed to identify a specific “memory-like” subset with the NK cell markers used. Moreover, in patients in relapse we found basically the same NK populations that those found at diagnostic, suggesting that NK cells equally respond to the first or second tumor rise. Finally, previous CMV infection largely affects the tumor-associated changes in NK population, but the CMV-associated CD57+NKG2C+ NK population does not look like to play any role. Funding Statement: The imaging facility MRI, member of the national infrastructure France BioImaging is supported by the French National Research Agency (ANR-10-INBS-04, «Investments for the future»). The “Region Languedoc Roussillon” supports the clinical data and samples (HEMODIAG_2020). This work was supported by the PRT-K program 2018 (MV and GC; 2018-021) and Canceropole GSO Emergence (MV; 2018/2019). This work was also supported by La Ligue Regionale contre le Cancer (GC), the “Investissements d’avenir” Grant LabEx MAbImprove: ANR-10-LABX-53 (GC/MV) and the NK 001 projet financed by the “Fonds Europeen de Developpement Regional “ (FEDER-FSE-IEJ 2014/2020) and by “Region Occitanie Pyrenees Mediterranee”. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The use of human specimens for scientific purposes was approved by the French National Ethics Committee. All methods were carried out in accordance with the approved guidelines and regulations of this committee. Written informed consent was obtained from each patient or donor prior to surgery.