Evidence map›Paper›PMID 34185709›Full record

ArticleJCI insight2021

Proteogenomic identification of an immunogenic HLA class I neoantigen in mismatch repair-deficient colorectal cancer tissue.

Tomomi Hirama, Serina Tokita, Munehide Nakatsugawa, Kenji Murata, Yasuhito Nannya, Kazuhiko Matsuo, Hidetoshi Inoko, Yoshihiko Hirohashi, Shinichi Hashimoto, Seishi Ogawa and 5 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.1field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 31 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 2 countries.

Tomomi HiramaDepartment of Pathology, Sapporo Medical University, Sapporo, Japan.
Serina TokitaDepartment of Pathology, Sapporo Medical University, Sapporo, Japan.
Munehide NakatsugawaDepartment of Pathology, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan.
Kenji MurataDepartment of Pathology, Sapporo Medical University, Sapporo, Japan.
Yasuhito NannyaDepartment of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Kazuhiko MatsuoSapporo Clinical Laboratory, Sapporo, Japan.
Hidetoshi InokoGenoDive Pharma Inc., Atsugi, Japan.
Yoshihiko HirohashiDepartment of Pathology, Sapporo Medical University, Sapporo, Japan.
Shinichi HashimotoDepartment of Molecular Pathophysiology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan.
Seishi OgawaDepartment of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Ichiro TakemasaDepartment of Surgery, Surgical Oncology and Science, Sapporo Medical University, Sapporo, Japan.
Noriyuki SatoDepartment of Pathology, Sapporo Medical University, Sapporo, Japan.
Fumitake HataSapporo Dohto Hospital, Sapporo, Japan.
Takayuki KanasekiDepartment of Pathology, Sapporo Medical University, Sapporo, Japan.
Toshihiko TorigoeDepartment of Pathology, Sapporo Medical University, Sapporo, Japan.
Sapporo Medical University · JPKyoto University · JPSapporo Science Center · JPTokyo Medical University Hachioji Medical Center · JPWakayama Medical University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although CD8+ T cells recognize neoantigens that arise from somatic mutations in cancer, only a small fraction of nonsynonymous mutations give rise to clinically relevant neoantigens. In this study, HLA class I ligandomes of a panel of human colorectal cancer (CRC) and matched normal tissues were analyzed using mass spectrometry-based proteogenomic analysis. Neoantigen presentation was rare; however, the analysis detected a single neoantigen in a mismatch repair-deficient CRC (dMMR-CRC) tissue sample carrying 3967 nonsynonymous mutations, where abundant tumor-infiltrating lymphocytes (TILs) and inflamed gene expression status were observed in the tumor microenvironment (TME). Using the HLA class I ligandome data and gene expression profiles, a set of nonmutated tumor-associated antigen (TAA) candidates was concomitantly identified. Interestingly, CD8+ TILs predominantly recognized the detected neoantigen over the array of TAA candidates. Neoantigen-reactive CD8+ TILs showed PD-1 positivity and exhibited functional and specific responses. Moreover, T cell receptor (TCR) profiling identified the sequence of the neoantigen-reactive TCR clonotype and showed its expansion in the TME. Transduction of the sequenced TCR conferred neoantigen specificity and cytotoxicity to peripheral blood lymphocytes. The proteogenomic approach revealed the antigenic and reactive T cell landscape in dMMR-CRC, demonstrating the presence of an immunogenic neoantigen and its potential therapeutic applications.

Indexed as

AdenocarcinomaAntigens, NeoplasmCD8-Positive T-LymphocytesCell Line, TumorColorectal NeoplasmsDNA Mismatch RepairHEK293 CellsHistocompatibility Antigens Class IHumansLymphocytes, Tumor-InfiltratingMutationProteogenomicsReceptors, Antigen, T-CellRNA-SeqTumor MicroenvironmentAntigens, NeoplasmHistocompatibility Antigens Class IReceptors, Antigen, T-CellCancer immunotherapyImmunology

Identifiers

PMID34185709
PMCPMC8410045
OpenAlexW3176465425

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.