下一代基于抗体的癌症治疗:抗体-药物偶联物和双特异性抗体在血液系统恶性肿瘤和实体瘤中的应用
Next-generation antibody-based therapeutics in cancer: antibody-drug conjugates bispecific antibodies across hematologic malignancies and solid tumors
肿瘤学的治疗范式正在经历由抗体药物偶联物(ADC)和双特异性抗体(bsAb)驱动的深刻变革。
英文原题:B lymphocytes and tertiary lymphoid structures have a prognostic impact on penile squamous cell carcinoma.
TLSs内高数量的肿瘤浸润B细胞是pSCC的一个有利预后标志物。
几种预后标志物,包括最近在阴茎鳞状细胞癌(pSCC)中发现的TIL(肿瘤浸润淋巴细胞),主要集中于T细胞。B细胞和三级淋巴结构(TLSs)的预后作用尚未得到充分描述。我们对全组织切片进行了TLSs的组织病理学检查,并对CD20和CD138进行了免疫组化检查。B细胞免疫评分(B-IS)根据这两种B细胞/浆细胞标志物(分别为CD20和CD138)的表达将队列分为五个类别。TLSs较少的患者总生存期(OS)较差[风险比(HR)= 2.17;95% CI:0.94-5;p = 0.069]。TLS直径较大与淋巴细胞浸润的存在之间存在显著关联[比值比(OR)= 2.2442;95% CI:1.1022-4.55;p = 0.0208]。低B-IS(HR = 1.89,95% CI:1.18-3.03,p = 0.008)、肿瘤中心CD20 + 细胞数量低(HR = 1.67,95% CI:1.04-2.7,p = 0.035)以及肿瘤浸润前沿CD20 + 细胞数量低(HR = 1.69,95% CI:1.06-2.78;p = 0.028)的患者OS显著较差。高B-IS与免疫组化检测到的突变型p53谱强相关(OR = 4.76,95% CI:1.32-25,p = 0.011)、低T细胞免疫评分(OR = 0.49;95% CI:0.23-1.03;p = 0.051)以及活跃的淋巴细胞浸润(OR = 2.0417,95% CI:1.01-4.76;p = 0.037)。浸润前沿CD20 + 细胞计数高与组织学3级疾病相关(OR = 2.44,95% CI 1.15-5.26,p = 0.015)。还观察到低B-IS与KMT2D(OR 0.31,95% CI:0.07-1.21,p = 0.057)和EGFR(OR = ∞,95% CI:0.86-∞,p = 0.053)突变之间存在关联。总之,TLS内高数量的肿瘤浸润B细胞是pSCC的一个有利预后标志物。这些发现强调需要在病理评估中识别新的微观预后标志物,以指导早期和适当的治疗策略。
Several prognostic markers, including tumor-infiltrating lymphocytes, which have been recently identified in penile squamous cell carcinoma (pSCC), have focused mostly on T cells. The prognostic role of B cells and tertiary lymphoid structures (TLSs) has not yet been sufficiently described. We examined whole tissue sections histopathologically for TLSs and immunohistochemically for CD20 and CD138. The B-cell immunoscore (B-IS) divided the cohort into five categories based on the expression of these two B-cell/plasma cell markers (CD20 and CD138, respectively). Patients with fewer TLSs had worse overall survival (OS) [hazard ratio (HR) = 2.17; 95% CI: 0.94-5; p = 0.069]. A significant association was identified between a high TLS diameter and the presence of a lymphocytic infiltrate [odds ratio (OR) = 2.2442; 95% CI: 1.1022-4.55; p = 0.0208]. Patients with low B-IS (HR = 1.89, 95% CI: 1.18-3.03, p = 0.008), a low number of CD20 + cells in the tumor center (HR = 1.67, 95% CI: 1.04-2.7, p = 0.035), and a low number of CD20 + cells at the tumor invasion front (HR = 1.69, 95% CI: 1.06-2.78; p = 0.028) had significantly worse OS. High B-ISs were strongly associated with a mutated p53 profile detected by immunohistochemistry (OR = 4.76, 95% CI: 1.32-25, p = 0.011), low T-cell immunoscores (OR = 0.49; 95% CI: 0.23-1.03; p = 0.051), and brisk lymphocytic infiltration (OR = 2.0417, 95% CI: 1.01-4.76; p = 0.037). High CD20 + cell counts at the invasion front were associated with histological grade 3 disease (OR = 2.44, 95% CI 1.15-5.26, p = 0.015). An association was also observed between low B-IS and mutations in KMT2D (OR 0.31, 95% CI: 0.07-1.21, p = 0.057) and EGFR (OR = ∞, 95% CI: 0.86-∞, p = 0.053). In conclusion, high numbers of tumor-infiltrating B cells within TLSs represent a favorable prognostic marker in pSCC. These findings emphasize the need to identify novel microscopic prognostic markers during pathological assessment to guide early and appropriate therapeutic strategies.
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