1. 免疫检测点抑制剂

1.1 HLA-1 genotype influences response to checkpoint inhibitors

Now, an analysis of the HLA class 1 genotypes of 1,535 patients with advanced-stage cancer (predominantly melanoma or non-small-cell lung cancer) receiving immune-checkpoint inhibition reveals associations between specific germline HLA genotypes and outcomes.

Statistically significant associations were observed between HLA homozygosity, even at a single HLA locus, and inferior overall survival outcomes in both cohorts of patients. Similarly, patients with a loss of HLA heterozygosity observed in tumour DNA also had inferior outcomes.

The more diverse your HLA genes, the better you will do！

HLA基因多样性越高，免疫检测点抑制剂治疗效果越好。纯合性高，杂合性缺失，预后较差。

• Chowell, D. et al. Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy. Science http://dx.doi.org/10.1126/ science.aao4572 (2017)
• HLA-1 genotype influences response to checkpoint inhibitors. Nature Reviews Clinical Oncology. 3 Jan 2018; doi:10.1038/nrclinonc.2017.210

1.2 dMMR presents opportunities to enhance immunotherapy

Tumours with DNA mismatch repair deficiency (dMMR) often develop and progress rapidly, but are paradoxically associated with a favourable prognosis.

dMMR increased mutability and concomitantly augmented the neoantigen burden. By contrast, the mutational load and neoantigen profile of the MMR-proficient cells remained stable.

drugs that might trigger dMMR, such as temozolomide.

错配修复缺陷：突变增加且抗原随着增加，免疫治疗效果更好。

错配修复正常：突变和抗原稳定。

• Germano, G. et al. Inactivation of DNA repair triggers neoantigen generation and impairs tumour growth. Nature 552, 116–120 (2017)
• dMMR presents opportunities to enhance immunotherapy. Nature Reviews Clinical Oncology. 19 Dec 2017; doi:10.1038/nrclinonc.2017.203