TY - JOUR T1 - Characterization of the Immunological Status of Hypermutated Solid Tumors in the Cancer Genome Analysis Project HOPE JF - Anticancer Research JO - Anticancer Res SP - 3537 LP - 3549 DO - 10.21873/anticanres.15840 VL - 42 IS - 7 AU - YASUTO AKIYAMA AU - RYOTA KONDOU AU - AKIRA IIZUKA AU - HARUO MIYATA AU - CHIE MAEDA AU - AKARI KANEMATSU AU - TADASHI ASHIZAWA AU - TAKESHI NAGASHIMA AU - KENICHI URAKAMI AU - YUJI SHIMODA AU - KEIICHI OHSHIMA AU - AKIO SHIOMI AU - YASUHISA OHDE AU - MASANORI TERASHIMA AU - KATSUHIKO UESAKA AU - YASUYUKI HIRASHIMA AU - YOSHIO KIYOHARA AU - HIROHISA KATAGIRI AU - TAKASHI SUGINO AU - AKIFUMI NOTSU AU - KEITA MORI AU - MITSURU TAKAHASHI AU - HIROTSUGU KENMOTSU AU - KEN YAMAGUCHI Y1 - 2022/07/01 UR - http://ar.iiarjournals.org/content/42/7/3537.abstract N2 - Background: 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. Patients and Methods: 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). Results: 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 CD8+ T-cells, activated effector CD8+ T-cells and natural killer cells were significantly higher in the TMB-H group. The T-cell receptor repertoire numbers and the diversity evenness score (DE50) were lower in the TMB-H group than in TMB-UL group; however, no association of the DE50 value with the binding or elution affinity of epitope peptides from neoantigens was found. Conclusion: One 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. ER -