Gut肿瘤相关巨噬细胞来源的CXCL8通过胃癌自主表达PD-L1表达决定

Paper Reading

Tumour-associated macrophages-derived CXCL8 determines immune evasion through autonomous PD-L1 expression in gastric cancer

Chao Lin et al Gut

As we know, immune checkpoint inhibitors showed promising efficacy and manageable safety in patients with gastric cancer, in this paper,the authors wants to discuss about the crosstalk

between

myeloid

cells

and

adaptive

immunity.Firstly,they suggested that high CXCL8 protein level in patients with gastric cancer was associated with short OS and they found that found that CXCL8 was predominantly secreted by macrophages based on results of FACS, and colony stimulating factor 2 (cSF-2) facilitates macrophage-derived cXcl8 secretion.Because of the phenomenon that CXCL8 contributes to immunosuppressive microenvironment, They observed that PD-

L1 was overexpressed in CXCL8high tumours by TCGA database.After that,they used the inhibitor to treated the suspension,and found that blocking CXCL8 pathway may promote antitumour immunity, accordingly, high levels of CXCL8+ macrophages are positively correlated with poor prognosis in patients with gastric cancer.Thus,they put up that CXCL8 inhibitors may drive antitumour response, providing potential therapeutic effects for patients with gastric cancer.

/pubmed/30661053

A neoantigen fitness model predicts tumour response to checkpoint blockade immunotherapy

Marta Łuksza, et al.

Nature

As we know,tumor can evolve resistance mechanisms by using checkpoint blockade molecules to disrupt the processes of immune recognition and attack,however,not all patients benefit from this therapy.The authors of this paper put up with neoantigens, which are tumour-specific, mutated peptides presented on the surface of cancer cells. They presented a fitness model for tumours based on immune interactions of neoantigens that predicts response to immunotherapy.What’s more,they also estimate the intrinsic probability of a neoantigen being recognized by a TCR.They estimate these components using the relative MHC binding affinity of each neoantigen to its wild type and a nonlinear dependence on sequence similarity of neoantigens to known antigens. Then,they also evaluate its fitness as a weighted effect of dominant neoantigens in the subclones of the tumor to describe the evolution of a heterogeneous tumor.About the disease model，they checked the survival in anti-CTLA-4-treated patients with melanoma and anti-PD-1-treated patients with lung cancer.They believed that using an immune fitness model to study immunotherapy could reveal broad similarities between the evolution of tumours and rapidly evolving pathogens.

/pubmed/29132144 Edited by Biaolong Deng