Peraldi Marie-Noëlle, Berrou Jeannig, Venot Marion, Chardiny Victor, Durrbach Antoine, Vieillard Vincent, Debré Patrice, Charron Dominique, Suberbielle Caroline, Chevret Sylvie, Glotz Denis, Dulphy Nicolas, Toubert Antoine
Transplantation. 2015 Nov;99(11):2422-30. doi: 10.1097/tp.0000000000000792.
The incidence of cancer is increased after solid organ transplantation. Natural killer (NK) cells are key effectors of the tumor immune response.
We conducted a cross sectional multicentre matched case-control study including 42 kidney transplant recipients (KTRs) on diagnosis of cancer and 41 KTRs without cancer. Extensive phenotyping of NK cells populations and functional tests of NK cells were performed.
Kidney transplant recipients with cancer had a higher incidence of acute rejection (P = 0.02) and cytomegalovirus (CMV) infection (P = 0.03) than controls. They had more lymphopenia than control KTRs (1020/mm3 +/- 32 vs 1218/mm3 +/- 34; P = 0.001) including a CD4+ lymphopenia (P = 0.01). Total CD3-/CD56+ NK cell counts were similar in both groups. However, KTRs with cancer had a lower frequency of the cytokine-enriched CD56bright NK cell subset (P = 0.001). The percentage of NK cells expressing NKp46 was decreased in KTRs with cancer (45% vs 53 %, P = 0.001). Furthermore, the ability of NK cells to degranulate CD107a+ cytolytic vesicles was reduced (11% vs 22%; P = 0.02), and the percentage of NK cells secreting IFN[gamma] was decreased (7.5% vs 28.8%; P = 0.01) in KTRs with cancer.
These results reveal an imbalance between NK cell subpopulations and functional NK cell defects in KTRs at the diagnosis of malignancy, including a decreased expression of NKp46 and decreased numbers of NK cells producing INF[gamma]. This study highlights the role of NKp46, a major activating NK cell receptor, which could be considered as a potential marker during immunological follow-up of KTRs.
实体器官移植后癌症发病率会升高。自然杀伤（NK）细胞是肿瘤免疫反应的关键效应细胞。
我们进行了一项横断面多中心匹配病例对照研究，纳入42例诊断为癌症的肾移植受者（KTR）和41例未患癌症的KTR。对NK细胞群体进行了广泛的表型分析，并对NK细胞进行了功能测试。
患癌的肾移植受者急性排斥反应（P = 0.02）和巨细胞病毒（CMV）感染（P = 0.03）的发生率高于对照组。他们的淋巴细胞减少情况比对照KTR更严重（1020/mm³ ± 32 vs 1218/mm³ ± 34；P = 0.001），包括CD4⁺淋巴细胞减少（P = 0.01）。两组的总CD3⁻/CD56⁺ NK细胞计数相似。然而，患癌的KTR中富含细胞因子的CD56bright NK细胞亚群的频率较低（P = 0.001）。患癌的KTR中表达NKp46的NK细胞百分比降低（45%对53%，P = 0.001）。此外，患癌的KTR中NK细胞脱颗粒产生CD107a⁺溶细胞囊泡的能力降低（11%对22%；P = 0.02），分泌IFNγ的NK细胞百分比降低（7.5%对28.8%；P = 0.01）。
这些结果揭示了在诊断恶性肿瘤时，KTR中NK细胞亚群之间存在失衡以及NK细胞功能缺陷，包括NKp46表达降低和产生INFγ的NK细胞数量减少。本研究强调了NKp46这一主要的活化NK细胞受体的作用，它可被视为KTR免疫随访期间的潜在标志物。
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