Spatial Profiles of Intratumoral PD-1+ Helper T Cells Predict Prognosis in Head and Neck Squamous Cell Carcinoma

Kanako Yoshimura; Takahiro Tsujikawa; Takahiro Tsujikawa; Junichi Mitsuda; Hiroshi Ogi; Hiroshi Ogi; Sumiyo Saburi; Gaku Ohmura; Akihito Arai; Saya Shibata; Guillaume Thibault; Young Hwan Chang; Young Hwan Chang; Young Hwan Chang; Daniel R. Clayburgh; Daniel R. Clayburgh; Satoru Yasukawa; Satoru Yasukawa; Aya Miyagawa-Hayashino; Eiichi Konishi; Kyoko Itoh; Lisa M. Coussens; Lisa M. Coussens; Shigeru Hirano

doi:10.3389/fimmu.2021.769534

Frontiers in Immunology (Oct 2021)

Spatial Profiles of Intratumoral PD-1+ Helper T Cells Predict Prognosis in Head and Neck Squamous Cell Carcinoma

Kanako Yoshimura,
Takahiro Tsujikawa,
Takahiro Tsujikawa,
Junichi Mitsuda,
Hiroshi Ogi,
Hiroshi Ogi,
Sumiyo Saburi,
Gaku Ohmura,
Akihito Arai,
Saya Shibata,
Guillaume Thibault,
Young Hwan Chang,
Young Hwan Chang,
Young Hwan Chang,
Daniel R. Clayburgh,
Daniel R. Clayburgh,
Satoru Yasukawa,
Satoru Yasukawa,
Aya Miyagawa-Hayashino,
Eiichi Konishi,
Kyoko Itoh,
Lisa M. Coussens,
Lisa M. Coussens,
Shigeru Hirano

Affiliations

Kanako Yoshimura: Department of Otolaryngology–Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
Takahiro Tsujikawa: Department of Otolaryngology–Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
Takahiro Tsujikawa: Department of Cell, Developmental & Cancer Biology, Oregon Health and Science University, Portland, OR, United States
Junichi Mitsuda: Department of Otolaryngology–Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
Hiroshi Ogi: Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Hiroshi Ogi: SCREEN Holdings Co., Ltd., Kyoto, Japan
Sumiyo Saburi: Department of Otolaryngology–Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
Gaku Ohmura: Department of Otolaryngology–Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
Akihito Arai: Department of Otolaryngology–Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
Saya Shibata: SCREEN Holdings Co., Ltd., Kyoto, Japan
Guillaume Thibault: Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, United States
Young Hwan Chang: Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, United States
Young Hwan Chang: Department of Computational Biology, Oregon Health and Science University, Portland, OR, United States
Young Hwan Chang: Knight Cancer Institute, Oregon Health and Science University, Portland, OR, United States
Daniel R. Clayburgh: Knight Cancer Institute, Oregon Health and Science University, Portland, OR, United States
Daniel R. Clayburgh: Department of Otolaryngology–Head and Neck Surgery, Oregon Health and Science University, Portland, OR, United States
Satoru Yasukawa: Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Satoru Yasukawa: 0Department of Pathology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan
Aya Miyagawa-Hayashino: Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Eiichi Konishi: Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Kyoko Itoh: Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Lisa M. Coussens: Department of Cell, Developmental & Cancer Biology, Oregon Health and Science University, Portland, OR, United States
Lisa M. Coussens: Knight Cancer Institute, Oregon Health and Science University, Portland, OR, United States
Shigeru Hirano: Department of Otolaryngology–Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan

DOI: https://doi.org/10.3389/fimmu.2021.769534
Journal volume & issue: Vol. 12

Abstract

Read online

BackgroundFunctional interactions between immune cells and neoplastic cells in the tumor immune microenvironment have been actively pursued for both biomarker discovery for patient stratification, as well as therapeutic anti-cancer targets to improve clinical outcomes. Although accumulating evidence indicates that intratumoral infiltration of immune cells has prognostic significance, limited information is available on the spatial infiltration patterns of immune cells within intratumoral regions. This study aimed to understand the intratumoral heterogeneity and spatial distribution of immune cell infiltrates associated with cell phenotypes and prognosis in head and neck squamous cell carcinoma (HNSCC).MethodsA total of 88 specimens of oropharyngeal squamous cell carcinoma, categorized into discovery (n = 38) and validation cohorts (n = 51), were analyzed for immune contexture by multiplexed immunohistochemistry (IHC) and image cytometry-based quantification. Tissue segmentation was performed according to a mathematical morphological approach using neoplastic cell IHC images to dissect intratumoral regions into tumor cell nests versus intratumoral stroma.ResultsTissue segmentation revealed heterogeneity in intratumoral T cells, varying from tumor cell nest-polarized to intratumoral stroma-polarized distributions. Leukocyte composition analysis revealed higher ratios of TH1/TH2 in tumor cell nests with higher percentages of helper T cells, B cells, and CD66b+ granulocytes within intratumoral stroma. A discovery and validation approach revealed a high density of programmed death receptor-1 (PD-1)+ helper T cells in tumor cell nests as a negative prognostic factor for short overall survival. CD163+ tumor-associated macrophages (TAM) provided the strongest correlation with PD-1+ helper T cells, and cases with a high density of PD-1+ helper T cells and CD163+ TAM had a significantly shorter overall survival than other cases.ConclusionThis study reveals the significance of analyzing intratumoral cell nests and reports that an immune microenvironment with a high density of PD-1+ helper T cells in tumoral cell nests is a poor prognostic factor for HNSCC.

Published in Frontiers in Immunology

ISSN: 1664-3224 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: http://journal.frontiersin.org/journal/immunology

About the journal

Abstract

Keywords