肿瘤细胞治疗研究
英文原题：Immune and pathologic responses in patients with localized prostate cancer who received daratumumab (anti-CD38) or edicotinib (CSF-1R inhibitor).
Immune and pathologic responses in patients with localized prostate cancer who received daratumumab (anti-CD38) or edicotinib (CSF-1R inhibitor).
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
达雷妥尤单抗和依地考替尼治疗在局限性前列腺癌患者中安全且耐受性良好，但未诱导 pCR。使用达雷妥尤单抗后，在前列腺肿瘤、骨髓和 PBMCs 中观察到 CD38+免疫细胞减少，但使用依地考替尼后未一致观察到 CSF-1R+免疫细胞的变化。单独使用任一髓系靶向药物均不足以在前列腺癌中产生抗肿瘤反应；因此，需要与诱导 T 细胞浸润的药物（如 ICTs）联合使用，以克服免疫抑制性前列腺 TME。
前列腺肿瘤微环境（TME）具有免疫抑制性，效应T细胞稀少，抑制性免疫细胞群富集，导致对免疫检查点治疗（ICT）等疗法的应答有限。前列腺TME的免疫组成在软组织和骨之间有所不同，而骨是最常见的治疗难治性转移部位。理解前列腺TME特有的免疫抑制机制将有助于制定合理的免疫治疗策略，以产生有效的抗肿瘤免疫应答。Daratumumab（抗CD38抗体）和edicotinib（集落刺激因子-1受体（CSF-1R）抑制剂）可能改变前列腺TME内的平衡，从而促进抗肿瘤免疫应答。假设：Daratumumab或edicotinib将是安全的，并将改变免疫TME，从而在局限性前列腺癌中产生抗肿瘤应答。
在这项术前研究中，局限性前列腺癌患者在根治性前列腺切除术（RP）前接受4周每周一次的daratumumab或4周每日一次的edicotinib治疗。对接受治疗和未接受治疗的对照组（前列腺活检Gleason评分≥8）前列腺切除标本以及患者匹配的治疗前后外周血单核细胞（PBMCs）和骨髓样本进行了评估。主要终点为不良事件（AEs）发生率。次要终点为病理完全缓解（pCR）率。
25例患者接受了治疗（daratumumab，n=15；edicotinib，n=10）。所有患者均未延迟接受RP。daratumumab组有3例患者（12%）发生3级治疗相关AE，edicotinib组未发生≥3级治疗相关AE。未观察到血清前列腺特异性抗原（PSA）水平变化或pCR。daratumumab导致前列腺肿瘤、骨髓和PBMCs中CD38+ T细胞、NK 细胞和髓系细胞频率降低。edicotinib未使前列腺、骨髓或PBMCs中CSF-1R+免疫细胞发生一致变化。两种治疗均未诱导T细胞浸润至前列腺TME。
The prostate tumor microenvironment (TME) is immunosuppressive, with few effector T cells and enrichment of inhibitory immune populations, leading to limited responses to treatments such as immune checkpoint therapies (ICTs). The immune composition of the prostate TME differs across soft tissue and bone, the most common site of treatment-refractory metastasis. Understanding immunosuppressive mechanisms specific to prostate TMEs will enable rational immunotherapy strategies to generate effective antitumor immune responses. Daratumumab (anti-CD38 antibody) and edicotinib (colony-stimulating factor-1 receptor (CSF-1R) inhibitor) may alter the balance within the prostate TME to promote antitumor immune responses. HYPOTHESIS: Daratumumab or edicotinib will be safe and will alter the immune TME, leading to antitumor responses in localized prostate cancer.
In this presurgical study, patients with localized prostate cancer received 4 weekly doses of daratumumab or 4 weeks of daily edicotinib prior to radical prostatectomy (RP). Treated and untreated control (Gleason score ≥8 in prostate biopsy) prostatectomy specimens and patient-matched pre- and post-treatment peripheral blood mononuclear cells (PBMCs) and bone marrow samples were evaluated. The primary endpoint was incidence of adverse events (AEs). The secondary endpoint was pathologic complete remission (pCR) rate.
Twenty-five patients were treated (daratumumab, n=15; edicotinib, n=10). All patients underwent RP without delays. Grade 3 treatment-related AEs with daratumumab occurred in 3 patients (12%), and no ≥grade 3 treatment-related AEs occurred with edicotinib. No changes in serum prostate-specific antigen (PSA) levels or pCRs were observed. Daratumumab led to a decreased frequency of CD38 + T cells, natural killer cells, and myeloid cells in prostate tumors, bone marrow, and PBMCs. There were no consistent changes in CSF-1R + immune cells in prostate, bone marrow, or PBMCs with edicotinib. Neither treatment induced T cell infiltration into the prostate TME.
Daratumumab and edicotinib treatment was safe and well-tolerated in patients with localized prostate cancer but did not induce pCRs. Decreases in CD38 + immune cells were observed in prostate tumors, bone marrow, and PBMCs with daratumumab, but changes in CSF-1R + immune cells were not consistently observed with edicotinib. Neither myeloid-targeted agent alone was sufficient to generate antitumor responses in prostate cancer; thus, combinations with agents to induce T cell infiltration (eg, ICTs) will be needed to overcome the immunosuppressive prostate TME.
MEMBER ACCOUNT
登录成功会直接打开下一页。
