Increased tumor-infiltrating lymphocyte density is associated with favorable outcomes in a comparative study of canine histiocytic sarcoma.
Increased tumor-infiltrating lymphocyte density is associated with favorable outcomes in a comparative study of canine histiocytic sarcoma.
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DOI：
10.1007/s00262-021-03033-z
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Atherton MJ
中科院分区：
文献类型：
--
作者：
Lenz JA;Assenmacher CA;Costa V;Louka K;Rau S;Keuler NS;Zhang PJ;Maki RG;Durham AC;Radaelli E;Atherton MJ
组织细胞肉瘤 (HS) 是一种罕见的侵袭性人类肿瘤，尚无普遍认可的护理治疗标准。自发性犬 HS 在特定品种中表现出患病率增加，与人类疾病具有关键的遗传和生物学相似性，并且发生在免疫功能健全的环境中。先前的数据暗示了这两种疾病的免疫原性，强调了免疫疗法成功治疗它们的潜力。对 5 例人类 HS 病例中 CD3 肿瘤浸润淋巴细胞 (TIL) 的定量显示，肿瘤内 T 细胞浸润存在差异。由于人类病例很少，并且缺乏当前的模型系统来评估 HS 抗肿瘤免疫与治疗结果之间的关联，我们分析了 18 只狗的临床数据并量化了 TIL，这些狗先前被诊断为局部 HS，并在有或没有辅助化疗的情况下接受了治愈性肿瘤切除术。与人类一样，对诊断时活检组织中的 TIL 进行评估揭示了一系列免疫学上“冷”到“热”的肿瘤。重要的是，我们发现 CD3 和颗粒酶 B TIL 的增加与手术切除后狗的良好结果呈正相关。 NanoString 转录分析显示，T 细胞和抗原呈递转录本的增加与犬肺 HS 的生存期延长相关，而肿瘤免疫原性的降低与脾 HS 的生存期缩短相关。基于这些发现，我们认为犬自发性 HS 是一种易于使用且功能强大的肿瘤免疫学研究新模型，并将提供一个独特的平台来临床前评估 HS 抗癌免疫疗法的疗效和耐受性。对人和犬的组织细胞肉瘤活检组织进行 T 细胞浸润分析。肿瘤浸润淋巴细胞密度的增加与治疗后结局的改善相关。
Histiocytic sarcoma (HS) is a rare and aggressive tumor in humans with no universally agreed Standard of care therapy. Spontaneous canine HS exhibits increased prevalence in specific breeds, shares key genetic and biologic similarities with the human disease, and occurs in an immunocompetent setting. Previous data alludes to the immunogenicity of this disease in both species, highlighting the potential for their successful treatment with immunotherapy. Quantification of CD3 tumor infiltrating lymphocytes (TIL) in five cases of human HS revealed variable intra-tumoral T cell infiltration. Due to the paucity of human cases and lack of current model systems in which to appraise associations between anti-tumor immunity and treatment-outcome in HS, we analyzed clinical data and quantified TIL in 18 dogs that were previously diagnosed with localized HS and treated with curative-intent tumor resection with or without adjuvant chemotherapy. As in humans, assessment of TIL in biopsy tissues taken at diagnosis reveal a spectrum of immunologically “cold” to “hot” tumors. Importantly, we show that increased CD3 and granzyme B TIL are positively associated with favorable outcomes in dogs following surgical resection. NanoString transcriptional analyses revealed increased T cell and antigen presentation transcripts associated with prolonged survival in canine pulmonary HS and a decreased tumor immunogenicity profile associated with shorter survivals in splenic HS. Based on these findings, we propose that spontaneous canine HS is an accessible and powerful novel model to study tumor immunology and will provide a unique platform to preclinically appraise the efficacy and tolerability of anti-cancer immunotherapies for HS. Human and canine histiocytic sarcoma biopsies were analyzed for T cell infiltrates. Increased density of tumor infiltrating lymphocytes was associated with improved outcomes following curative-incent treatment.
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影响因子：
2.4
作者：
Affolter, VK;Moore, PF
通讯作者：
Moore, PF
DOI：
10.1038/nrc.2016.97
发表时间：
2016-08-23
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Fesnak AD;June CH;Levine BL
通讯作者：
Levine BL
影响因子：
3.1
作者：
Abadie, Jerome;Hedan, Benoit;Andre, Catherine
通讯作者：
Andre, Catherine
影响因子：
--
作者：
Gatalica, Zoran;Bilalovic, Nurija;Arceci, Robert J.
通讯作者：
Arceci, Robert J.
影响因子：
7.3
作者：
Galon, Jerome;Mlecnik, Bernhard;Bindea, Gabriela;Angell, Helen K.;Berger, Anne;Lagorce, Christine;Lugli, Alessandro;Zlobec, Inti;Hartmann, Arndt;Bifulco, Carlo;Nagtegaal, Iris D.;Palmqvist, Richard;Masucci, Giuseppe V.;Botti, Gerardo;Tatangelo, Fabiana;Delrio, Paolo;Maio, Michele;Laghi, Luigi;Grizzi, Fabio;Asslaber, Martin;D'Arrigo, Corrado;Vidal-Vanaclocha, Fernando;Zavadova, Eva;Chouchane, Lotfi;Ohashi, Pamela S.;Hafezi-Bakhtiari, Sara;Wouters, Bradly G.;Roehrl, Michael;Nguyen, Linh;Kawakami, Yutaka;Hazama, Shoichi;Okuno, Kiyotaka;Ogino, Shuji;Gibbs, Peter;Waring, Paul;Sato, Noriyuki;Torigoe, Toshihiko;Itoh, Kyogo;Patel, Prabhu S.;Shukla, Shilin N.;Wang, Yili;Kopetz, Scott;Sinicrope, Frank A.;Scripcariu, Viorel;Ascierto, Paolo A.;Marincola, Francesco M.;Fox, Bernard A.;Pages, Franck
通讯作者：
Pages, Franck