Oncolytic adenovirus promotes vascular normalization and nonclassical tertiary lymphoid structure formation through STING-mediated DC activation

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ABSTRACT

Inducing a full antitumor immune response in the tumor microenvironment (TME) is essential for successful cancer immunotherapy. Here, we report that an oncolytic adenovirus carrying mIL-15 (Ad-IL15) can effectively induce antitumor immune response and inhibit tumor growth in a mouse model of cancer. We found that Ad-IL15 facilitated the activation and infiltration of immune cells, including dendritic cells (DCs), T cells and natural killer (NK) cells, in the TME. Unexpectedly, we observed that Ad-IL15 also induced vascular normalization and tertiary lymphoid structure formation in the TME. Moreover, we demonstrated these Ad-IL15-induced changes in the TME were depended on the Ad-IL15-induced activation of the STING-TBK1-IRF3 pathway in DCs. Taken together, our findings suggest that Ad-IL15 is a candidate for cancer immunotherapy that promotes immune cell activation and infiltration, tumor vascular normalization and tertiary lymphoid structure formation in the TME.

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Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)

This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.

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TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells.

Taiwen Li, Jingyu Fan, Binbin Wang … (2017)

Recent clinical successes of cancer immunotherapy necessitate the investigation of the interaction between malignant cells and the host immune system. However, elucidation of complex tumor-immune interactions presents major computational and experimental challenges. Here, we present Tumor Immune Estimation Resource (TIMER; cistrome.shinyapps.io/timer) to comprehensively investigate molecular characterization of tumor-immune interactions. Levels of six tumor-infiltrating immune subsets are precalculated for 10,897 tumors from 32 cancer types. TIMER provides 6 major analytic modules that allow users to interactively explore the associations between immune infiltrates and a wide spectrum of factors, including gene expression, clinical outcomes, somatic mutations, and somatic copy number alterations. TIMER provides a user-friendly web interface for dynamic analysis and visualization of these associations, which will be of broad utilities to cancer researchers. Cancer Res; 77(21); e108-10. ©2017 AACR.

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TIMER2.0 for analysis of tumor-infiltrating immune cells

Taiwen Li, Jingxin Fu, Zexian Zeng … (2020)

Abstract Tumor progression and the efficacy of immunotherapy are strongly influenced by the composition and abundance of immune cells in the tumor microenvironment. Due to the limitations of direct measurement methods, computational algorithms are often used to infer immune cell composition from bulk tumor transcriptome profiles. These estimated tumor immune infiltrate populations have been associated with genomic and transcriptomic changes in the tumors, providing insight into tumor–immune interactions. However, such investigations on large-scale public data remain challenging. To lower the barriers for the analysis of complex tumor–immune interactions, we significantly improved our previous web platform TIMER. Instead of just using one algorithm, TIMER2.0 (http://timer.cistrome.org/) provides more robust estimation of immune infiltration levels for The Cancer Genome Atlas (TCGA) or user-provided tumor profiles using six state-of-the-art algorithms. TIMER2.0 provides four modules for investigating the associations between immune infiltrates and genetic or clinical features, and four modules for exploring cancer-related associations in the TCGA cohorts. Each module can generate a functional heatmap table, enabling the user to easily identify significant associations in multiple cancer types simultaneously. Overall, the TIMER2.0 web server provides comprehensive analysis and visualization functions of tumor infiltrating immune cells.

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Author and article information

Journal

Journal ID (nlm-ta): Oncoimmunology

Journal ID (iso-abbrev): Oncoimmunology

Title: Oncoimmunology

Publisher: Taylor & Francis

ISSN (Print): 2162-4011

ISSN (Electronic): 2162-402X

Publication date (Electronic, pub): 1 July 2022

Publication date (Electronic, collection): 2022

Publication date PMC-release: 1 July 2022

Volume: 11

Issue: 1

Electronic Location Identifier: 2093054

Affiliations

[a ]Department of Infectious Diseases, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University; , Hangzhou, Zhejiang, China

[b ]Department of Thoracic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University; , Hangzhou, Zhejiang, China

[c ]Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University; , Hangzhou, Zhejiang, China

[d ]Department of Emergency, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University; , Hangzhou, Zhejiang, China

Author notes

CONTACT Pin Wu pinwu@ 123456zju.edu.cn Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University; , Hangzhou, Zhejiang, China

Feng Xu xufeng99@ 123456zju.edu.cn Department of Infectious Diseases, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University; , Hangzhou, Zhejiang, 310009, China

[#]

These authors contributed equally to this work

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Publisher ID: 2093054

DOI: 10.1080/2162402X.2022.2093054

PMC ID: 9255224

PubMed ID: 35800155

SO-VID: f7a7d67f-ff71-49f8-a0e6-dad78e3c1a2f

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This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Oncolytic adenovirus promotes vascular normalization and nonclassical tertiary lymphoid structure formation through STING-mediated DC activation

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Gamma Delta T cells

Most cited references 65

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells.

TIMER2.0 for analysis of tumor-infiltrating immune cells

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