Two immune-enhanced molecular subtypes differ in inflammation, checkpoint signaling and outcome of advanced head and neck squamous cell carcinoma
The immune environment of primary tumor is associated with the clinical response and benefit of immunotherapy. This study aims to investigate the intratumoral immune profile and its clinical relevance in advanced head and neck squamous cell carcinoma (HNSCC). Gene expression profiles of 401 HNSCCs a...
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Online Access: | http://dx.doi.org/10.1080/2162402X.2017.1392427 |
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doaj-d734ffb968cf47d5a150e7b49a271d292020-11-25T03:51:26ZengTaylor & Francis GroupOncoImmunology2162-402X2018-02-017210.1080/2162402X.2017.13924271392427Two immune-enhanced molecular subtypes differ in inflammation, checkpoint signaling and outcome of advanced head and neck squamous cell carcinomaBangrong Cao0Qifeng Wang1Huan Zhang2Guiquan Zhu3Jinyi Lang4University of Electronic Science and Technology of ChinaUniversity of Electronic Science and Technology of ChinaUniversity of Electronic Science and Technology of ChinaUniversity of Electronic Science and Technology of ChinaUniversity of Electronic Science and Technology of ChinaThe immune environment of primary tumor is associated with the clinical response and benefit of immunotherapy. This study aims to investigate the intratumoral immune profile and its clinical relevance in advanced head and neck squamous cell carcinoma (HNSCC). Gene expression profiles of 401 HNSCCs at stage III-IVB from two cohorts (The Cancer Genome Atlas, TCGA, n = 203; the Leipzig Head and Neck Group, LHNG, n = 198) were involved in this analysis. Based on the global immune-related genes, four gene expression subtypes (C1-4) were identified in HNSCCs. Overall, subtypes C2 and C3 showed upregulation of immune profiles and increased tumor lymphocyte infiltration, exhibiting an enhanced immune microenvironment (EIME). However, the two EIME subtypes revealed differences in immune markers and clinical features. Subtype C2 showed higher expression of macrophage signature, whereas subtype C3 was more associated with B cell infiltration. T cell and NK cell infiltration was not different between C2 and C3 subtypes. The subtype C2 tumors were characterized by inflammation compared with subtype C3. Although the checkpoint receptors PD1 and CTLA4 expressed equally between the EIME subtypes, their ligands (PD-L1/PD-L2, CD86/CD80) were significantly upregulated in subtype C2 compared with C3. HPV-positive tumors were predominantly enriched in subtype C3 but not in C2. Furthermore, patients in subtype C2 had a worse outcome than those in C3. In summary, two immune-enhanced subtypes with different immune characteristics and clinical features were identified in advanced HNSCC. The different immune microenvironments among HNSCC subgroups may provide new insights into the strategy of immunotherapy.http://dx.doi.org/10.1080/2162402X.2017.1392427hnsccmolecular subtypeinflammationimmune checkpoint pathwayhpv |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bangrong Cao Qifeng Wang Huan Zhang Guiquan Zhu Jinyi Lang |
spellingShingle |
Bangrong Cao Qifeng Wang Huan Zhang Guiquan Zhu Jinyi Lang Two immune-enhanced molecular subtypes differ in inflammation, checkpoint signaling and outcome of advanced head and neck squamous cell carcinoma OncoImmunology hnscc molecular subtype inflammation immune checkpoint pathway hpv |
author_facet |
Bangrong Cao Qifeng Wang Huan Zhang Guiquan Zhu Jinyi Lang |
author_sort |
Bangrong Cao |
title |
Two immune-enhanced molecular subtypes differ in inflammation, checkpoint signaling and outcome of advanced head and neck squamous cell carcinoma |
title_short |
Two immune-enhanced molecular subtypes differ in inflammation, checkpoint signaling and outcome of advanced head and neck squamous cell carcinoma |
title_full |
Two immune-enhanced molecular subtypes differ in inflammation, checkpoint signaling and outcome of advanced head and neck squamous cell carcinoma |
title_fullStr |
Two immune-enhanced molecular subtypes differ in inflammation, checkpoint signaling and outcome of advanced head and neck squamous cell carcinoma |
title_full_unstemmed |
Two immune-enhanced molecular subtypes differ in inflammation, checkpoint signaling and outcome of advanced head and neck squamous cell carcinoma |
title_sort |
two immune-enhanced molecular subtypes differ in inflammation, checkpoint signaling and outcome of advanced head and neck squamous cell carcinoma |
publisher |
Taylor & Francis Group |
series |
OncoImmunology |
issn |
2162-402X |
publishDate |
2018-02-01 |
description |
The immune environment of primary tumor is associated with the clinical response and benefit of immunotherapy. This study aims to investigate the intratumoral immune profile and its clinical relevance in advanced head and neck squamous cell carcinoma (HNSCC). Gene expression profiles of 401 HNSCCs at stage III-IVB from two cohorts (The Cancer Genome Atlas, TCGA, n = 203; the Leipzig Head and Neck Group, LHNG, n = 198) were involved in this analysis. Based on the global immune-related genes, four gene expression subtypes (C1-4) were identified in HNSCCs. Overall, subtypes C2 and C3 showed upregulation of immune profiles and increased tumor lymphocyte infiltration, exhibiting an enhanced immune microenvironment (EIME). However, the two EIME subtypes revealed differences in immune markers and clinical features. Subtype C2 showed higher expression of macrophage signature, whereas subtype C3 was more associated with B cell infiltration. T cell and NK cell infiltration was not different between C2 and C3 subtypes. The subtype C2 tumors were characterized by inflammation compared with subtype C3. Although the checkpoint receptors PD1 and CTLA4 expressed equally between the EIME subtypes, their ligands (PD-L1/PD-L2, CD86/CD80) were significantly upregulated in subtype C2 compared with C3. HPV-positive tumors were predominantly enriched in subtype C3 but not in C2. Furthermore, patients in subtype C2 had a worse outcome than those in C3. In summary, two immune-enhanced subtypes with different immune characteristics and clinical features were identified in advanced HNSCC. The different immune microenvironments among HNSCC subgroups may provide new insights into the strategy of immunotherapy. |
topic |
hnscc molecular subtype inflammation immune checkpoint pathway hpv |
url |
http://dx.doi.org/10.1080/2162402X.2017.1392427 |
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