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Heterogeneity and evolution of tumour immune microenvironment in metastatic gastroesophageal adenocarcinoma.


ABSTRACT:

Background

Tumour immune microenvironment heterogeneity is prevalent in numerous cancers and can negatively impact immunotherapy response. Immune heterogeneity and evolution in gastroesophageal adenocarcinoma (GEA) have not been studied in the past.

Methods

Together with a multi-region sampling of normal, primary and metastatic tissues, we performed whole exome sequencing, TCR sequencing as well as immune cell infiltration estimation through deconvolution of gene expression signals.

Results

We discovered high TCR repertoire and immune cell infiltration heterogeneity among metastatic sites, while they were homogeneous among primary and normal samples. Metastatic sites shared high levels of abundant TCR clonotypes with blood, indicating immune surveillance via blood. Metastatic sites also had low levels of tumour-eliminating immune cells and were undergoing heavy immunomodulation compared to normal and primary tumour tissues. There was co-evolution of neo-antigen and TCR repertoire, but only in patients with late diverging mutational evolution. Co-evolution of TCR repertoire and immune cell infiltration was seen in all except one patient.

Conclusions

Our findings revealed immune heterogeneity and co-evolution in GEA, which may inform immunotherapy decision-making.

SUBMITTER: Wang W 

PROVIDER: S-EPMC9587966 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Heterogeneity and evolution of tumour immune microenvironment in metastatic gastroesophageal adenocarcinoma.

Wang Wei W   Ye Liu-Fang LF   Bao Hua H   Hu Ming-Tao MT   Han Ming M   Tang Hai-Meng HM   Ren Chao C   Wu Xue X   Shao Yang Y   Wang Feng-Hua FH   Zhou Zhi-Wei ZW   Li Yu-Hong YH   Xu Rui-Hua RH   Wang De-Shen DS  

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 20220729 6


<h4>Background</h4>Tumour immune microenvironment heterogeneity is prevalent in numerous cancers and can negatively impact immunotherapy response. Immune heterogeneity and evolution in gastroesophageal adenocarcinoma (GEA) have not been studied in the past.<h4>Methods</h4>Together with a multi-region sampling of normal, primary and metastatic tissues, we performed whole exome sequencing, TCR sequencing as well as immune cell infiltration estimation through deconvolution of gene expression signal  ...[more]

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