Exploration of the immunogenetic landscape of hyperprogressive disease after combined immunotherapy in cancer patients

Caifeng Gong; Wen Zhang; Yongkun Sun; Jianzhong Shou; Zhichao Jiang; Tianyi Liu; Shengzhou Wang; Jun Liu; Ying Sun; Aiping Zhou

doi:10.1016/j.isci.2023.106720

Exploration of the immunogenetic landscape of hyperprogressive disease after combined immunotherapy in cancer patients

iScience. 2023 Apr 23;26(6):106720. doi: 10.1016/j.isci.2023.106720. eCollection 2023 Jun 16.

Authors

Affiliations

¹ Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
² Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
³ GenomiCare Biotechnology Co. Ltd, Shanghai 201203, China.

Abstract

The immune-genetic changes that occur in cancer patients experiencing hyperprogressive disease (HPD) during combined immunotherapy are unclear. In this study, HPD patients with pre- and post-HPD samples and non-HPD patients with solid tumors were molecularly characterized by genetic and tumor immune microenvironment (TiME) analyses of paired samples by whole-exome sequencing, RNA sequencing, and multiplex immunofluorescence. The genetic analysis of paired samples showed that almost all the tumor driver gene mutations were preserved between pre- and post-HPD tumors. HPD patients had higher frequencies of mutations in TP53 and CNN2, and a significantly higher mutant-allele tumor heterogeneity than non-HPD patients. Tumor IL-6 mRNA was upregulated in post-HPD samples vs. pre-HPD, accompanied by a potential immune suppressive TiME with an elevated M2/M1 ratio. Salvage treatment with irinotecan plus bevacizumab was effective in one HPD patient, who experienced prolonged survival. These genetic features and TiME characteristics might help identify the features of HPD after immunotherapy.

Keywords: Clinical finding; Health sciences; Medical informatics; Oncology.