Efficacy and side effects of immune checkpoint inhibitors in the treatment of colorectal cancer.
Efficacy and side effects of immune checkpoint inhibitors in the treatment of colorectal cancer.
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DOI：
10.1177/17562848211002018
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发表时间：
2021
影响因子：
4.2
通讯作者：
Scharl M
中科院分区：
文献类型：
--
作者：
Manz SM;Losa M;Fritsch R;Scharl M
结直肠癌（CRC）仍然是西方世界最常见和最具挑战性的肿瘤之一。免疫治疗方法在晚期CRC亚组中的应答率是显著的，并且可持续地改变了治疗方案。不幸的是，目前可用的免疫治疗剂仅在微卫星不稳定性高（MSI-H）/DNA错配修复缺陷（dMMR）CRC中显示出显著的抗肿瘤活性-在无进展生存期（PFS）和客观缓解率（ORR）方面。随后，这些显著的结果导致美国食品和药物管理局批准免疫检查点抑制剂（ICI）pembrolizumab和nivolumab用于治疗晚期MSI-H/dMMR CRC。然而，在微卫星稳定（MSS）/DNA错配修复熟练（pMMR）CRC中，ICI显然未能满足他们的期望，因此被认为无效。由于绝大多数CRC表现出分子MSS/pMMR谱，目前的治疗方法奋进改善肿瘤免疫原性，这连续导致促炎细胞因子水平以及肿瘤浸润T细胞增加，而这些细胞又可以被各种免疫抑制剂靶向。因此，正在进行的研究正在研究新型协同治疗方式和方法，以克服MSS/pMMR CRC中“冷”到“热”的肿瘤转化。本文综述了ICI治疗MSI-H/dMMR和MSS/pMMR CRC的疗效、可能的免疫相关不良事件以及新的治疗方法。
Colorectal cancers (CRCs) remain one of the most common and challenging neoplasia in the Western world. The response rate of immunotherapeutic treatment approaches in a subset of advanced CRCs is remarkable and has sustainably changed treatment regimens. Unfortunately, currently available immunotherapeutics only displayed significant antitumoral activity – in terms of progression free survival (PFS) and objective response rate (ORR) – in microsatellite instability-high (MSI-H)/DNA mismatch repair deficient (dMMR) CRCs. Subsequently, these remarkable results had led to the US Food and Drug Administration’s approval of both immune checkpoint inhibitors (ICIs) pembrolizumab and nivolumab in the treatment of advanced MSI-H/dMMR CRCs. However, in microsatellite stable (MSS)/DNA mismatch repair proficient (pMMR) CRCs, ICIs have clearly failed to meet their expectations and are therefore not considered effective. As the vast majority of CRCs display a molecular MSS/pMMR profile, current treatment approaches endeavor to improve tumor immunogenicity that consecutively leads to increased proinflammatory cytokine levels as well as tumor infiltrating T-cells, which in turn may be targeted by various immunotherapeutic agents. Therefore, ongoing studies are investigating novel synergistic therapy modalities and approaches to overcome a “cold” to “hot” tumor conversion in MSS/pMMR CRCs. In this review, we summarize the efficacy and possible immune-related adverse events as well as novel therapeutic approaches of ICIs in the treatment of MSI-H/dMMR and MSS/pMMR CRCs.
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PD-1和PD-L1检查点信号传导抑制癌症免疫疗法：机制，组合和临床结果。
影响因子：
5.6
作者：
Alsaab HO;Sau S;Alzhrani R;Tatiparti K;Bhise K;Kashaw SK;Iyer AK
通讯作者：
Iyer AK
影响因子：
50.3
作者：
Hanahan, Douglas;Coussens, Lisa M.
通讯作者：
Coussens, Lisa M.
影响因子：
9.1
作者：
Eiro, Noemi;Gonzalez, Lucia;Vizoso, Francisco J.
通讯作者：
Vizoso, Francisco J.
DOI：
10.1634/theoncologist.2020-0356
发表时间：
2020-11
期刊：
The oncologist
影响因子：
--
作者：
Guo Y;Guo XL;Wang S;Chen X;Shi J;Wang J;Wang K;Klempner SJ;Wang W;Xiao M
通讯作者：
Xiao M
影响因子：
7.3
作者：
Galon, Jerome;Mlecnik, Bernhard;Bindea, Gabriela;Angell, Helen K.;Berger, Anne;Lagorce, Christine;Lugli, Alessandro;Zlobec, Inti;Hartmann, Arndt;Bifulco, Carlo;Nagtegaal, Iris D.;Palmqvist, Richard;Masucci, Giuseppe V.;Botti, Gerardo;Tatangelo, Fabiana;Delrio, Paolo;Maio, Michele;Laghi, Luigi;Grizzi, Fabio;Asslaber, Martin;D'Arrigo, Corrado;Vidal-Vanaclocha, Fernando;Zavadova, Eva;Chouchane, Lotfi;Ohashi, Pamela S.;Hafezi-Bakhtiari, Sara;Wouters, Bradly G.;Roehrl, Michael;Nguyen, Linh;Kawakami, Yutaka;Hazama, Shoichi;Okuno, Kiyotaka;Ogino, Shuji;Gibbs, Peter;Waring, Paul;Sato, Noriyuki;Torigoe, Toshihiko;Itoh, Kyogo;Patel, Prabhu S.;Shukla, Shilin N.;Wang, Yili;Kopetz, Scott;Sinicrope, Frank A.;Scripcariu, Viorel;Ascierto, Paolo A.;Marincola, Francesco M.;Fox, Bernard A.;Pages, Franck
通讯作者：
Pages, Franck