Resistance Mechanisms to Immune-Checkpoint Blockade in Cancer: Tumor-Intrinsic and -Extrinsic Factors

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• 作者：Jonathan M. Pitt¹ ; ² ; ³ ; Marie Vé ; tizou¹ ; ² ; ³ ; Romain Daillè ; re¹ ; ² ; ³ ; Marí ; a Paula Roberti¹ ; ² ; Takahiro Yamazaki¹ ; ² ; Bertrand Routy¹ ; ² ; ³ ; Patricia Lepage⁴ ; Ivo Gomperts Boneca⁵ ; ⁶ ; Mathias Chamaillard⁷ ; Guido Kroemer⁸ ; ⁹ ; ¹⁰ ; ¹¹ ; ¹² ; ¹³ ; ¹⁴ ; Laurence Zitvogel¹ ; ² ; ³ ; ¹⁵ ; ^{laurence.zitvogel@gustaveroussy.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：immune-checkpoint blockade ; immunotherapy ; microbiota ; cancer ; PD-1 ; PD-L1 ; ipilimumab ; CTLA-4 ; microbiome ; immunotherapy resistance
• 刊名：Immunity
• 出版年：2016
• 出版时间：21 June 2016
• 年：2016
• 卷：44
• 期：6
• 页码：1255-1269
• 全文大小：1900 K

文摘

Inhibition of immune regulatory checkpoints, such as CTLA-4 and the PD-1-PD-L1 axis, is at the forefront of immunotherapy for cancers of various histological types. However, such immunotherapies fail to control neoplasia in a significant proportion of patients. Here, we review how a range of cancer-cell-autonomous cues, tumor-microenvironmental factors, and host-related influences might account for the heterogeneous responses and failures often encountered during therapies using immune-checkpoint blockade. Furthermore, we describe the emerging evidence of how the strong interrelationship between the immune system and the host microbiota can determine responses to cancer therapies, and we introduce a concept by which prior or concomitant modulation of the gut microbiome could optimize therapeutic outcomes upon immune-checkpoint blockade.