Dataset Information

Fewer tumour-specific PD-1⁺CD8⁺ TILs in high-risk "Infiltrating" HPV^- HNSCC.

ABSTRACT:

Background

The prognosis of HPV^- HNSCC was worse than that of HPV⁺ HNSCC. Analysis of tumours and tumour-infiltrating lymphocytes (TILs) may provide insight into the progression of HPV^- HNSCC.

Methods

The tumour and TIL phenotypic characteristics of 134 HNSCC specimens (HPV^- tumours were classified into "Infiltrating" and "Pushing" subtypes based on their different tumour nest configuration and prognosis) were retrospectively analysed. HNSCC data from the Cancer Genome Atlas (n = 263) were analysed for CD8α, HPV and overall survival (OS). A murine HNSCC model was used to verify the antitumour role of PD-1⁺CD8⁺ TILs.

Results

The "Infiltrating" HPV^- subtype showed shorter OS than the "Pushing" subtype. Moreover, there is a tendency from "Pushing" to "Infiltrating" subtype from the primary to the recurrent lesion. Different from total CD8⁺ TILs, tumour-specific PD-1⁺CD8⁺ TILs were fewer in invasive margin (IM) of "Infiltrating" HPV^- tumours. PD-1⁺CD8⁺ TILs recognised autologous HNSCC cells and showed stronger inhibition of tumour growth in a murine HNSCC model resistant to PD-1 blockade.

Conclusions

Coevolution of HPV^- HNSCC and TILs is characterised by an "Infiltrating" phenotype and less tumour-specific PD-1⁺CD8⁺ TILs, which may provide a framework for further translational studies and patient stratification.

SUBMITTER: Xu K

PROVIDER: S-EPMC7492364 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Fewer tumour-specific PD-1<sup>+</sup>CD8<sup>+</sup> TILs in high-risk "Infiltrating" HPV<sup>-</sup> HNSCC.

Xu Ke K Fu You Y Han Yong Y Xia Ronghui R Xu Shengming S Duan Shengzhong S Zhang Zhiyuan Z Li Jiang J

British journal of cancer 20200703 6

<h4>Background</h4>The prognosis of HPV<sup>-</sup> HNSCC was worse than that of HPV<sup>+</sup> HNSCC. Analysis of tumours and tumour-infiltrating lymphocytes (TILs) may provide insight into the progression of HPV<sup>-</sup> HNSCC.<h4>Methods</h4>The tumour and TIL phenotypic characteristics of 134 HNSCC specimens (HPV<sup>-</sup> tumours were classified into "Infiltrating" and "Pushing" subtypes based on their different tumour nest configuration and prognosis) were retrospectively analysed. H ...[more]

PMID: 32616847

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Project description:T cells are important in tumour immunity but a better understanding is needed of the differentiation of antigen-specific T cells in human cancer1,2. Here we studied CD8 T cells in patients with human papillomavirus (HPV)-positive head and neck cancer and identified several epitopes derived from HPV E2, E5 and E6 proteins that allowed us to analyse virus-specific CD8 T cells using major histocompatibility complex (MHC) class I tetramers. HPV-specific CD8 T cells expressed PD-1 and were detectable in the tumour at levels that ranged from 0.1% to 10% of tumour-infiltrating CD8 T lymphocytes (TILs) for a given epitope. Single-cell RNA-sequencing analyses of tetramer-sorted HPV-specific PD-1+ CD8 TILs revealed three transcriptionally distinct subsets. One subset expressed TCF7 and other genes associated with PD-1+ stem-like CD8 T cells that are critical for maintaining T cell responses in conditions of antigen persistence. The second subset expressed more effector molecules, representing a transitory cell population, and the third subset was characterized by a terminally differentiated gene signature. T cell receptor clonotypes were shared between the three subsets and pseudotime analysis suggested a hypothetical differentiation trajectory from stem-like to transitory to terminally differentiated cells. More notably, HPV-specific PD-1+TCF-1+ stem-like TILs proliferated and differentiated into more effector-like cells after in vitro stimulation with the cognate HPV peptide, whereas the more terminally differentiated cells did not proliferate. The presence of functional HPV-specific PD-1+TCF-1+CD45RO+ stem-like CD8 T cells with proliferative capacity shows that the cellular machinery to respond to PD-1 blockade exists in HPV-positive head and neck cancer, supporting the further investigation of PD-1 targeted therapies in this malignancy. Furthermore, HPV therapeutic vaccination efforts have focused on E6 and E7 proteins; our results suggest that E2 and E5 should also be considered for inclusion as vaccine antigens to elicit tumour-reactive CD8 T cell responses of maximal breadth.

Dataset Information

Fewer tumour-specific PD-1⁺CD8⁺ TILs in high-risk "Infiltrating" HPV^- HNSCC.

Background

Methods

Results

Conclusions

Publications

Fewer tumour-specific PD-1<sup>+</sup>CD8<sup>+</sup> TILs in high-risk "Infiltrating" HPV<sup>-</sup> HNSCC.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Fewer tumour-specific PD-1+CD8+ TILs in high-risk "Infiltrating" HPV- HNSCC.

Background

Methods

Results

Conclusions

Publications

Fewer tumour-specific PD-1<sup>+</sup>CD8<sup>+</sup> TILs in high-risk "Infiltrating" HPV<sup>-</sup> HNSCC.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Fewer tumour-specific PD-1⁺CD8⁺ TILs in high-risk "Infiltrating" HPV^- HNSCC.