We tested how adjuvants effect in a cancer vaccine model using an epitope derived from an autoactivation loop of membrane-type protease serine protease 14 (PRSS14; loop metavaccine) in mouse mammary tumor virus (MMTV)-polyoma middle tumor-antigen (PyMT) system and in 2 other orthotopic mouse systems. Earlier, we reported that loop metavaccine effectively prevented progression and metastasis regardless of adjuvant types and TH types of hosts in tail-vein injection systems. However, the loop metavaccine with Freund's complete adjuvant (CFA) reduced cancer progression and metastasis while that with alum, to our surprise, were adversely affected in 3 tumor bearing mouse models. The amounts of loop peptide specific antibodies inversely correlated with tumor burden and metastasis, meanwhile both TH1 and TH2 isotypes were present regardless of host type and adjuvant. Tumor infiltrating myeloid cells such as eosinophil, monocyte, and neutrophil were asymmetrically distributed among 2 adjuvant groups with loop metavaccine. Systemic expression profiling using the lymph nodes of the differentially immunized MMTV-PyMT mouse revealed that adjuvant types, as well as loop metavaccine can change the immune signatures. Specifically, loop metavaccine itself induces TH2 and TH17 responses but reduces TH1 and Treg responses regardless of adjuvant type, whereas CFA but not alum increased follicular TH response. Among the myeloid signatures, eosinophil was most distinct between CFA and alum. Survival analysis of breast cancer patients showed that eosinophil chemokines can be useful prognostic factors in PRSS14 positive patients. Based on these observations, we concluded that multiple immune parameters are to be considered when applying a vaccine strategy to cancer patients.

中文翻译：

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使用源自膜型蛋白酶 PRSS14 的结构表位对预防性抗转移疫苗的关键佐剂影响

我们使用衍生自膜型蛋白酶丝氨酸蛋白酶 14（PRSS14；环元疫苗）的自激活环的表位在小鼠乳腺肿瘤病毒 (MMTV)-多瘤中间肿瘤抗原 (PyMT) 系统中测试了佐剂在癌症疫苗模型中的作用以及其他 2 个原位小鼠系统。早些时候，我们报道了无论尾静脉注射系统中的佐剂类型和宿主的 TH 类型如何，环元疫苗都能有效地阻止进展和转移。然而，带有弗氏完全佐剂 (CFA) 的环元疫苗减少了癌症的进展和转移，而令我们惊讶的是，带有明矾的环元疫苗在 3 个荷瘤小鼠模型中受到不利影响。环肽特异性抗体的数量与肿瘤负荷和转移呈负相关，同时，无论宿主类型和佐剂如何，都存在 TH1 和 TH2 同种型。肿瘤浸润的髓系细胞，如嗜酸性粒细胞、单核细胞和中性粒细胞，不对称分布在具有环元疫苗的 2 个佐剂组中。使用差异免疫的 MMTV-PyMT 小鼠淋巴结的系统表达谱显示，佐剂类型以及环元疫苗可以改变免疫特征。具体而言，环元疫苗本身诱导 TH2 和 TH17 反应，但无论佐剂类型如何，都会降低 TH1 和 Treg 反应，而 CFA 而不是明矾增加滤泡 TH 反应。在骨髓特征中，嗜酸性粒细胞在 CFA 和明矾之间最为明显。乳腺癌患者的生存分析表明，嗜酸性粒细胞趋化因子可能是 PRSS14 阳性患者的有用预后因素。