High immunosuppressive burden in cancer patients: a major hurdle for cancer immunotherapy.
High immunosuppressive burden in cancer patients: a major hurdle for cancer immunotherapy.
复制标题
DOI：
10.1007/s00262-016-1810-0
复制
发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Thanavala Y
中科院分区：
文献类型：
--
作者：
Kalathil SG;Thanavala Y
癌症免疫治疗的一个瓶颈是肿瘤细胞所处的免疫抑制微环境。尽管通过主动免疫或过继转移可在患者体内产生大量肿瘤特异性T细胞，但这些T细胞在体内并不容易转化为对肿瘤细胞的杀伤。防止自身免疫的免疫调节机制可能被肿瘤细胞利用来逃避免疫破坏。调节性T细胞、髓源性抑制细胞、抑制性细胞因子和免疫检查点受体是免疫系统协同作用导致肿瘤微环境中抗肿瘤免疫被颠覆的主要成分。这种冗余的免疫抑制网络可能阻碍有效的免疫治疗，从而促进肿瘤进展。癌症进展清楚地表明了对肿瘤细胞无休止生长的免疫控制失败。详细了解这些造成免疫抑制屏障以保护肿瘤细胞免受免疫破坏的每个因素，对于开发基于免疫的新型癌症治疗干预措施至关重要。对这些抑制细胞进行多管齐下的靶向清除可能恢复CD8 + T细胞颗粒酶B的产生，并增加产生干扰素 - γ的CD4 + T细胞的数量。
A bottleneck for immunotherapy of cancer is the immunosuppressive microenvironment in which the tumor cells are located. Regardless of the fact that large numbers of tumor-specific T cells can be generated in patients by active immunization or adoptive transfer, these T cells do not readily translate to tumor cell killing in vivo. The immune regulatory mechanism which prevents autoimmunity may be harnessed by tumor cells for the evasion of immune destruction. Regulatory T cells, myeloid-derived suppressor cells, inhibitory cytokines and immune checkpoint receptors are the major components of the immune system acting in concert to cause the subversion of anti-tumor immunity in the tumor microenvironment. This redundant immunosuppressive network may pose an impediment to efficacious immunotherapy, thus facilitating tumor progression. Cancer progression clearly documents the failure of immune control over relentless growth of tumor cells. Detailed knowledge of each of these factors responsible for creating an immunosuppressive shield to protect tumor cells from immune destruction is essential for the development of novel immune based therapeutic interventions of cancer. Multi-pronged targeted depletion of these suppressor cells may restore production of granzyme B by CD8+ T cells and increase the number of IFN-γ producing CD4+ T cells.
登录
查看更多内容
DOI：
10.1056/nejmoa1504030
发表时间：
2015-07-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Larkin J;Chiarion-Sileni V;Gonzalez R;Grob JJ;Cowey CL;Lao CD;Schadendorf D;Dummer R;Smylie M;Rutkowski P;Ferrucci PF;Hill A;Wagstaff J;Carlino MS;Haanen JB;Maio M;Marquez-Rodas I;McArthur GA;Ascierto PA;Long GV;Callahan MK;Postow MA;Grossmann K;Sznol M;Dreno B;Bastholt L;Yang A;Rollin LM;Horak C;Hodi FS;Wolchok JD
通讯作者：
Wolchok JD
影响因子：
7.2
作者：
Lugade AA;Kalathil S;Miller A;Iyer R;Thanavala Y
通讯作者：
Thanavala Y
影响因子：
10.1
作者：
Hodi FS;Lawrence D;Lezcano C;Wu X;Zhou J;Sasada T;Zeng W;Giobbie-Hurder A;Atkins MB;Ibrahim N;Friedlander P;Flaherty KT;Murphy GF;Rodig S;Velazquez EF;Mihm MC Jr;Russell S;DiPiro PJ;Yap JT;Ramaiya N;Van den Abbeele AD;Gargano M;McDermott D
通讯作者：
McDermott D
DOI：
10.4049/jimmunol.1401572
发表时间：
2014-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ostrand-Rosenberg S;Horn LA;Haile ST
通讯作者：
Haile ST
影响因子：
11.2
作者：
Mao, Yumeng;Poschke, Isabel;Kiessling, Rolf
通讯作者：
Kiessling, Rolf