老年人比年輕人更可能患癌癥,老年人的身體往往往往不能不足以打腫瘤這一戰(zhàn),接受治療產(chǎn)生的毒副作用也較多,。
但圣安東尼奧得克薩斯大學(xué)健康科學(xué)中心大學(xué)癌癥治療和研究中心的研究表明:以前認(rèn)為某些只有在年輕患者體內(nèi)發(fā)揮作用的免疫類型也可以用來幫助老年腫瘤患者,。
醫(yī)藥衛(wèi)生科學(xué)中心公共衛(wèi)生碩士Tyler Curiel醫(yī)學(xué)博士、教授說:我們已經(jīng)證明,,免疫治療不僅對(duì)老年癌癥小鼠有效,,實(shí)際上免疫治療可能對(duì)老年癌癥患者也有效。相關(guān)研究論文發(fā)表在4月15日的Cancer Research雜志上,。
隨著年齡的增長(zhǎng),,人體的免疫系統(tǒng)會(huì)減弱,但它也發(fā)生了某些變化,,包括改變身體內(nèi)與疾病作斗爭(zhēng)的規(guī)則,。Curiel博士的研究小組抑制了關(guān)閉了促進(jìn)癌癥發(fā)展的免疫反應(yīng)中的調(diào)節(jié)性T細(xì)胞。調(diào)節(jié)性T細(xì)胞在癌癥的增加在年輕機(jī)體中,,抑制調(diào)節(jié)性T細(xì)胞活性的藥物使免疫系統(tǒng)能發(fā)揮更好的作用,。在老年機(jī)體中,即使藥物抑制了調(diào)節(jié)性T細(xì)胞,,該藥物也不會(huì)有臨床效益,。
在年紀(jì)較大的老鼠中,當(dāng)藥物抑制調(diào)節(jié)性T細(xì)胞后,,研究人員發(fā)現(xiàn)另一種類型的免疫抑制細(xì)胞(髓系衍生抑制細(xì)胞MDSC)頂替了調(diào)節(jié)性T細(xì)胞的地位,,阻礙了臨床療效。但上述現(xiàn)象這并不發(fā)生在年輕小鼠中,。團(tuán)隊(duì)添加了針對(duì)MDSC的第二個(gè)藥物后,,發(fā)現(xiàn)老年患者可以像年輕癌癥患者那樣對(duì)抗癌癥。
在黑色素瘤細(xì)胞研究中發(fā)現(xiàn)這些結(jié)果后,,研究人員考察了結(jié)腸癌中是否也存在同樣情況,。Curiel博士說:下一步是開展老年癌癥患者免疫治療臨床試驗(yàn),以驗(yàn)證這些研究結(jié)果,。(生物谷:Bioon.com)
doi:10.1158/0008-5472.CAN-11-3019
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Mitigating Age-Related Immune Dysfunction Heightens the Efficacy of Tumor Immunotherapy in Aged Mice
Vincent Hurez, Benjamin J. Daniel, Lishi Sun, Ai-Jie Liu, Sara M. Ludwig, Mark J. Kious, Suzanne R. Thibodeaux, Srilakshmi Pandeswara, Kruthi Murthy, et al.
Although cancer tends to affect the elderly, most preclinical studies are carried out in young subjects. In this study, we developed a melanoma-specific cancer immunotherapy that shows efficacy in aged but not young hosts by mitigating age-specific tumor-associated immune dysfunction. Both young and aged CD4+CD25hi regulatory T cells (Treg) exhibited equivalent in vitro T-cell suppression and tumor-associated augmentation in numbers. However, denileukin diftitox (DT)-mediated Treg depletion improved tumor-specific immunity and was clinically effective only in young mice. DT-mediated Treg depletion significantly increased myeloid-derived suppressor cell (MDSC) numbers in aged but not young mice, and MDSC depletion improved tumor-specific immunity and reduced tumor growth in aged mice. Combining Treg depletion with anti–Gr-1 antibody was immunologically and clinically more efficacious than anti–Gr-1 antibody alone in aged B16-bearing mice, similar to Treg depletion alone in young mice. In contrast, DT increased MDSCs in young and aged mice following MC-38 tumor challenge, although effects were greater in aged mice. Anti–Gr-1 boosted DT effects in young but not aged mice. Aged antitumor immune effector cells are therefore competent to combat tumor when underlying tumor-associated immune dysfunction is appropriately mitigated, but this dysfunction varies with tumor, thus also varying responses to immunotherapy. By tailoring immunotherapy to account for age-related tumor-associated immune dysfunctions, cancer immunotherapy for aged patients with specific tumors can be remarkably improved.