VAMC Research Service (151), Building 70, One Veterans Drive, Minneapolis, MN 55417 U.S.A.
Anticancer Res. 2013 Sep;33(9):3635-43.
Immune cells (lymphocytes and macrophages) provide the microenvironment for immune surveillance of metastatic prostate cancer (PCa) cells in pelvic lymph nodes. We have hypothesized that degeneration and/or apoptosis of metastatic PCa cells in pelvic lymph nodes can distinguish between aggressive and non-aggressive metastatic disease in patients. Our objective was to define the relationship between metastatic cell lysis and the presence of immune cells.
We studied archival primary PCa (n=38) and cancer-positive regional pelvic nodes (n=32) from the same patients undergoing radical retropubic prostatectomy at the Minneapolis Veterans Affairs Medical Center.
Using morphological and immunohistochemical features of immune and metastatic cancer cells, we have identified progression of metastasis in the nodal compartments. Nodal parenchyma contained small, intermediate and large metastatic nodules/tumors. Immune surveillance occurred primarily in small tumors and surveillance was either absent or greatly reduced in intermediate and large tumors in nodes. Metastatic nodules/cells were lysed or became apoptotic when under immune-surveillance, as indicated by pyknotic nuclei and cytoplasm, the latter still had remnants of prostate specific antigen (PSA) staining. Metastatic cells without surveillance did not exhibit morphological features of cell degeneration (lysis) or apoptosis. Metastatic cells under immune-surveillance had an inverse relationship with those without immune-surveillance. This relationship differed from node to node and patient to patient.
We have shown that at least two populations of metastatic cells were present in the nodes; the first group of cells was under immune surveillance, as indicated by limited to wide-spread cell lysis/apoptosis, and the second group did not exhibit morphological evidence of cell lysis indicating emergence of surveillance-unresponsive (resistant) metastatic cells. These criteria can be used to distinguish metastatic cancer that is expected to be responsive to immunotherapy from that which would show little or no benefit from such treatment. Enhancement of immune surveillance and other treatments can be used to treat surveillance-unresponsive (resistant) disease to improve survival of patients.
免疫细胞（淋巴细胞和巨噬细胞）为盆腔淋巴结中转移性前列腺癌（PCa）细胞的免疫监视提供了微环境。我们假设，盆腔淋巴结中转移性 PCa 细胞的退化和/或凋亡可以区分患者侵袭性和非侵袭性转移性疾病。我们的目的是定义转移性细胞溶解与免疫细胞存在之间的关系。
我们研究了来自明尼苏达州退伍军人事务医疗中心接受根治性耻骨后前列腺切除术的同一患者的存档原发性 PCa（n=38）和阳性癌症的盆腔区域淋巴结（n=32）。
使用免疫和转移性癌细胞的形态学和免疫组织化学特征，我们已经确定了淋巴结内转移的进展。淋巴结实质包含小、中、大转移性结节/肿瘤。免疫监视主要发生在小肿瘤中，而在淋巴结中的中、大肿瘤中，监视要么不存在，要么大大减少。当处于免疫监视下时，转移性结节/细胞被裂解或发生凋亡，表现为核固缩和细胞质，后者仍有前列腺特异性抗原（PSA）染色的残留物。没有监视的转移性细胞没有表现出细胞退化（裂解）或凋亡的形态特征。处于免疫监视下的转移性细胞与没有免疫监视的转移性细胞呈反比关系。这种关系因节点和患者而异。
我们已经表明，至少有两种转移性细胞群体存在于淋巴结中；第一组细胞受到免疫监视，表现为有限到广泛的细胞裂解/凋亡，第二组细胞没有表现出细胞裂解的形态学证据，表明出现了免疫监视无反应（耐药）的转移性细胞。这些标准可用于区分预期对免疫治疗有反应的转移性癌症与从这种治疗中获益甚少或没有获益的转移性癌症。增强免疫监视和其他治疗方法可用于治疗免疫监视无反应（耐药）疾病，以提高患者的生存率。
