Korbelik M, Dougherty G J
Cancer Imaging Department, British Columbia Cancer Agency, Vancouver, Canada.
Cancer Res. 1999 Apr 15;59(8):1941-6.
The curative ability of photodynamic therapy (PDT) is severely compromised if treated tumors are growing in immunodeficient hosts. Reconstitution of severe combined immunodeficient (scid) mice with splenocytes from naive immunologically intact BALB/c mice did not improve the response to Photofrin-based PDT of EMT6 tumors growing in these animals. In contrast, adoptive transfer of BALB/c splenocytes containing EMT6 tumor-sensitized immune cells had a dramatic effect on tumor regrowth after PDT. For instance, full restoration of the curative effect of PDT was achieved with scid mice that received splenocytes from BALB/c donors that were cured of EMT6 tumors by PDT 5 weeks before adoptive transfer. Splenocytes obtained from donors cured of EMT6 tumors using X-rays were much less effective. Selective in vitro depletion of specific T-cell populations from engrafting splenocytes indicated that CTLs are the main immune effector cells responsible for conferring the curative outcome to PDT in this experimental model, whereas helper T lymphocytes play a supportive role. The immune specificity of these T-cell populations was demonstrated by the absence of cross-reactivity between the EMT6 and Meth-A tumor models (mismatch between tumors growing in splenocyte donors and recipients). The immunocompetent BALB/c mice that received adoptively transferred splenocytes containing PDT-generated, tumor-sensitized immune cells also benefited from the improved outcome of PDT of tumors they were bearing. This was demonstrated not only with the fairly immunogenic EMT6 tumor model but also with weakly immunogenic Line 1 carcinomas. The results of this study indicate that PDT is a highly effective means of generating tumor-sensitized immune cells that can be recovered from lymphoid sites distant to the treated tumor at protracted time intervals after PDT, which asserts their immune memory character. It is also shown that the treatment of tumors by PDT creates the conditions necessary for converting the inactive adoptively transferred pre-effector, tumor-sensitized immune cells into fully functional antitumor effector cells. An additional finding of this study is the evidence of NK cell activation in PDT-treated Meth-A sarcomas.
如果待治疗的肿瘤在免疫缺陷宿主中生长，光动力疗法（PDT）的治疗能力将受到严重损害。用来自未接触过抗原的免疫健全的BALB/c小鼠的脾细胞重建严重联合免疫缺陷（scid）小鼠，并未改善这些动物体内生长的EMT6肿瘤对基于卟吩姆钠的PDT的反应。相比之下，过继转移含有对EMT6肿瘤致敏的免疫细胞的BALB/c脾细胞，对PDT后的肿瘤再生长有显著影响。例如，对于在过继转移前5周通过PDT治愈了EMT6肿瘤的BALB/c供体来源的脾细胞，接受这些脾细胞的scid小鼠实现了PDT治疗效果的完全恢复。从使用X射线治愈了EMT6肿瘤的供体获得的脾细胞效果要差得多。从植入的脾细胞中选择性体外去除特定T细胞群体表明，在该实验模型中，细胞毒性T淋巴细胞（CTL）是赋予PDT治疗效果的主要免疫效应细胞，而辅助性T淋巴细胞起支持作用。EMT6和Meth-A肿瘤模型之间不存在交叉反应（脾细胞供体和受体中生长的肿瘤不匹配），证明了这些T细胞群体的免疫特异性。接受过继转移的含有PDT产生的、对肿瘤致敏的免疫细胞的脾细胞的免疫健全的BALB/c小鼠，也从其自身所患肿瘤PDT效果的改善中受益。这不仅在免疫原性相当强的EMT6肿瘤模型中得到证实，在免疫原性弱的1号线癌中也得到了证实。这项研究的结果表明，PDT是一种产生对肿瘤致敏的免疫细胞的高效方法，这些免疫细胞在PDT后较长时间间隔内可从远离治疗肿瘤的淋巴部位回收，这证明了它们的免疫记忆特性。研究还表明，通过PDT治疗肿瘤创造了将无活性的过继转移前效应细胞、对肿瘤致敏的免疫细胞转化为功能完全的抗肿瘤效应细胞所需的条件。这项研究的另一个发现是在PDT治疗的Meth-A肉瘤中有自然杀伤（NK）细胞激活的证据。
