The in vitro elimination of virus-infected and tumor cells by NK cells is regulated by a balance between signals conveyed via specific inhibitory and activating receptors. Whether NK cells and specifically the NK-activating receptor NKp46 (NCR1 in mice) are directly involved in tumor eradication in vivo is still largely unknown. Since the NKp46/NCR1 tumor ligands have not been identified yet, we use a screening technique to identify functional ligands for NKp46/NCR1 which is based on a cell reporter assay and discover a NCR1 ligand in the PD1.6 lymphoma line. To study whether NKp46/NCR1 is important for the eradication of PD1.6 lymphoma in vivo, we used the Ncr1 knockout Ncr1gfp/gfp mice generated by our group. Strikingly, all Ncr1 knockout mice developed growing PD1.6 tumors, whereas initial tumor growth was observed in the wild-type mice and tumors were completely rejected as time progressed. The growth of other lymphoma cell lines such as B10 and EL4 was equivalent between the Ncr1 knockout and wild-type mice. Finally, we show that PD1.6 lymphoma cells are less killed both in vitro and in vivo in the absence of NKp46/NCR1. Our results therefore reveal a crucial role for NKp46/NCR1 in the in vivo eradication of some lymphoma cells.
128 Background: Breast cancer-related lymphedema (BCRL) affects the quality of life, but there is no consensus regarding early detection and monitoring. Patient-reported outcomes (PROs) are important in assessing cancer survivor outcomes. LYMPHA (Lymphatic Microsurgical Preventive Healing Approach) and S-LYMPHA (Simplified LYMPHA) have reduced BCRL rates. This study aims to identify the most reliable PRO in a South Florida multi-ethnic population and to study correlations between PROs and objective measurements in the first 6 months after axillary surgery. Methods: Patients aged 18 and above undergoing axillary lymph node dissection (ALND) or axillary radiation were included. L-Dex (Spectroscopy) and three validated questionnaires (LyQLI, Lymphedema Quality of Life Inventory; LyQOL, Lymphedema Quality of Life and FACT-B4+ Functional Assessment of Cancer Therapy-Lymphedema) were recorded at baseline and 6 months post-surgery to assess the association between patient-reported symptoms and BCRL. Lymphedema was defined as L-Dex score outside the normal range, or a 10 unit increase above baseline. Additional variables such as demographics, tumor characteristics, and treatment modalities were considered. Results: Out of 40 recruited patients, 39 were analysed (excluding one deceased patient). One patient was male. Amongst the females,18 were pre-menopausal and 20 were post-menopausal. Hispanic ethnicity was reported by 23 (58.9%) patients compared to 16 (41%) non-Hispanic. White race, African American and other races were reported in 31, 4, and 4 patients respectively. 1, 22, and 16 patients had Cancer stages 1, 2, and 3 respectively. Neo-adjuvant therapy (endocrine or chemotherapy) was administered to 31 patients; 13 and 26 patients had lumpectomy and mastectomy respectively. 18 patients had breast reconstruction. Patients were divided into three groups for analysis: 1) ALND with no axillary radiation (n=33,85%); 2) Sentinel Lymph Node Biopsy (SLNB) with axillary radiation (n=3,8%); 3) ALND with axillary radiation (n=3,8%). In the first group, LYMPHA or S-LYMPHA were associated with lower rates of lymphedema (19% vs, 50%) (p=0.116). No patients in the second or third groups had lymphedema. There were 4 out of 20 (20%) patients with lymphedema with scores above the median for FACT B4+ (p= 0.41) and a lower score (higher quality of life) correlated with lower L-Dex value (p=0.76). The higher score in the physical domain of LyQLI showed higher L-Dex vaue (p=0.826). There was a significant inter-domain correlation in LyQLI and LyQOL (p<0.05 to <0.001). Conclusions: These preliminary results validate the use of PROs alongside objective measurements to assess BCRL. In addition, LYMPHA and S-LYMPHA significantly reduce lymphedema rates. Larger numbers will be necessary to reach statistical significance and to identify the best PRO.
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