Inter-patient and intra-tumor heterogeneity in the sensitivity to tumor-targeted immunity in colorectal cancer

Tsubasa Miyauchi, Tomonori Yaguchi, Yutaka Kawakami

研究成果: Article

2 引用 (Scopus)

抄録

Efficacy of immune checkpoint inhibitors such as PD-1 antibody for colorectal cancer remains to be proved except in microsatellite- instability-high (MSI-H) cases. While the objective response rate of MSI-H cases was 40%, that of microsatellite-stable (MSS) cases was 0%, showing that response rate to immune checkpoint inhibitors varies even among the microsatellite status. Some possible mechanisms that confer each patient variation in the response to immunotherapy should be considered. We focused on the combination of inter-patient heterogeneity and intra-tumor heterogeneity as a determining factor of immune reaction. An example of intra-tumor heterogeneity is the low expression of tumor antigen by CD271+ cells in melanoma. It is not surprising that similar mechanism exists in CRC. Other related intra-tumor heterogeneity includes EMT and autophagy, both molecular mechanisms that are thought to promote immune-evading phenotype. Besides the microsatellite status, inter- patient heterogeneity in response to tumor immunity includes hypermutator phenotype, which is driven by POLE mutation, intrinsic cytokine production, and microbiota in the gut.

元の言語English
ページ(範囲)54-59
ページ数6
ジャーナルJapanese Journal of Clinical Immunology
40
発行部数1
DOI
出版物ステータスPublished - 2017

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Colorectal Neoplasms
Immunity
Microsatellite Repeats
Microsatellite Instability
Neoplasms
Phenotype
Autophagy
Immunologic Factors
Neoplasm Antigens
Immunotherapy
Melanoma
Cytokines
Mutation
Antibodies

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

これを引用

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abstract = "Efficacy of immune checkpoint inhibitors such as PD-1 antibody for colorectal cancer remains to be proved except in microsatellite- instability-high (MSI-H) cases. While the objective response rate of MSI-H cases was 40{\%}, that of microsatellite-stable (MSS) cases was 0{\%}, showing that response rate to immune checkpoint inhibitors varies even among the microsatellite status. Some possible mechanisms that confer each patient variation in the response to immunotherapy should be considered. We focused on the combination of inter-patient heterogeneity and intra-tumor heterogeneity as a determining factor of immune reaction. An example of intra-tumor heterogeneity is the low expression of tumor antigen by CD271+ cells in melanoma. It is not surprising that similar mechanism exists in CRC. Other related intra-tumor heterogeneity includes EMT and autophagy, both molecular mechanisms that are thought to promote immune-evading phenotype. Besides the microsatellite status, inter- patient heterogeneity in response to tumor immunity includes hypermutator phenotype, which is driven by POLE mutation, intrinsic cytokine production, and microbiota in the gut.",
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N2 - Efficacy of immune checkpoint inhibitors such as PD-1 antibody for colorectal cancer remains to be proved except in microsatellite- instability-high (MSI-H) cases. While the objective response rate of MSI-H cases was 40%, that of microsatellite-stable (MSS) cases was 0%, showing that response rate to immune checkpoint inhibitors varies even among the microsatellite status. Some possible mechanisms that confer each patient variation in the response to immunotherapy should be considered. We focused on the combination of inter-patient heterogeneity and intra-tumor heterogeneity as a determining factor of immune reaction. An example of intra-tumor heterogeneity is the low expression of tumor antigen by CD271+ cells in melanoma. It is not surprising that similar mechanism exists in CRC. Other related intra-tumor heterogeneity includes EMT and autophagy, both molecular mechanisms that are thought to promote immune-evading phenotype. Besides the microsatellite status, inter- patient heterogeneity in response to tumor immunity includes hypermutator phenotype, which is driven by POLE mutation, intrinsic cytokine production, and microbiota in the gut.

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