1. Characterization of the Immunological Status of Hypermutated Solid Tumors in the Cancer Genome Analysis Project HOPE
- Author
-
YASUTO AKIYAMA, RYOTA KONDOU, AKIRA IIZUKA, HARUO MIYATA, CHIE MAEDA, AKARI KANEMATSU, TADASHI ASHIZAWA, TAKESHI NAGASHIMA, KENICHI URAKAMI, YUJI SHIMODA, KEIICHI OHSHIMA, AKIO SHIOMI, YASUHISA OHDE, MASANORI TERASHIMA, KATSUHIKO UESAKA, YASUYUKI HIRASHIMA, YOSHIO KIYOHARA, HIROHISA KATAGIRI, TAKASHI SUGINO, AKIFUMI NOTSU, KEITA MORI, MITSURU TAKAHASHI, HIROTSUGU KENMOTSU, and KEN YAMAGUCHI
- Subjects
Cancer Research ,Oncology ,Neoplasms ,Mutation ,Biomarkers, Tumor ,Humans ,General Medicine ,CD8-Positive T-Lymphocytes ,Prognosis - Abstract
Many reports demonstrate that a high tumor mutation burden (TMB-H) is closely associated with good prognosis of cancer. However, specific studies investigating the association of various TMB statuses with overall survival in patients with solid tumors are scarce.In the present study, we investigated the association of TMB status with overall survival in 5,072 patients with cancer from the HOPE project and clarified the specific mechanism responsible for the good prognosis of the TMB-H group. All tumors were classified into one of four groups based on TMB: ultralow (UL), low (L), intermediate (I) and high (H).The TMB-H group had a better prognosis than the TMB-I and TMB-L groups, but not than the TMB-UL group. Analyzing the expression of 293 immune response-associated genes, 17 genes were up-regulated in the TMB-H group compared to the TMB-I and TNB-L groups, and two genes [CD274 and interferon-γ (IFNG)] were identified as good prognostic factors. Analysis of immune cell populations inside tumors demonstrated that the frequencies of exhausted CD8One possible mechanism for the good prognosis of the TMB-UL group compared to the TMB-H group might be that the TMB-UL group features a balance between immunosuppression and immunostimulation.
- Published
- 2022