Heterogeneity of the tumor immune microenvironment and its clinical relevance DOI Creative Commons
Qingzhu Jia, Aoyun Wang,

Yixiao Yuan

et al.

Experimental Hematology and Oncology, Journal Year: 2022, Volume and Issue: 11(1)

Published: April 23, 2022

During the course of tumorigenesis and subsequent metastasis, malignant cells gradually diversify become more heterogeneous. Consequently, tumor mass might be infiltrated by diverse immune-related components, including cytokine/chemokine environment, cytotoxic activity, or immunosuppressive elements. This immunological heterogeneity is universally presented spatially varies temporally along with evolution therapeutic intervention across almost all solid tumors. The anti-tumor immunity shows a profound association progression disease responsiveness to treatment, particularly in realm immunotherapy. Therefore, an accurate understanding essential for development effective therapies. Facilitated multi-regional -omics sequencing, single cell longitudinal liquid biopsy approaches, recent studies have demonstrated potential investigate complexity tumors its clinical relevance Here, we aimed review mechanism underlying immune microenvironment. We also explored how assessments facilitate personalized

Language: Английский

Nerves in cancer DOI
Ali H. Zahalka, Paul S. Frenette

Nature reviews. Cancer, Journal Year: 2020, Volume and Issue: 20(3), P. 143 - 157

Published: Jan. 23, 2020

Language: Английский

Citations

312
Senescence-Induced Vascular Remodeling Creates Therapeutic Vulnerabilities in Pancreas Cancer DOI Creative Commons
Marcus Ruscetti, John P. Morris, Riccardo Mezzadra

et al.

Cell, Journal Year: 2020, Volume and Issue: 181(2), P. 424 - 441.e21

Published: March 31, 2020

Language: Английский

Citations

310
Oncolytic viruses for cancer immunotherapy DOI Creative Commons
Otto Hemminki, João M. Santos, Akseli Hemminki

et al.

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: June 29, 2020

Abstract In this review, we discuss the use of oncolytic viruses in cancer immunotherapy treatments general, with a particular focus on adenoviruses. These serve as model to elucidate how versatile are, and they can be used complement other therapies gain optimal patient benefits. Historical reports from over hundred years suggest treatment efficacy safety adenovirus viruses. This is confirmed more contemporary series multiple clinical trials. Yet, while first have already been granted approval several regulatory authorities, room for improvement remains. As good tolerability seen, virus field has now moved increase wide array approaches. Adding different immunomodulatory transgenes one strategy gaining momentum. Immunostimulatory molecules thus produced at tumor reduced systemic side effects. On hand, preclinical work suggests additive or synergistic effects conventional such radiotherapy chemotherapy. addition, newly introduced checkpoint inhibitors drugs could make perfect companions Especially tumors that seem not recognized by immune system made immunogenic Logically, combination being evaluated ongoing Another promising avenue modulating microenvironment allow T cell solid tumors. Oncolytic next remarkable wave immunotherapy.

Language: Английский

Citations

265
Single-cell analysis of human non-small cell lung cancer lesions refines tumor classification and patient stratification DOI Creative Commons
Andrew M. Leader, John A. Grout, Bárbara Maier

et al.

Cancer Cell, Journal Year: 2021, Volume and Issue: 39(12), P. 1594 - 1609.e12

Published: Nov. 11, 2021

Language: Английский

Citations

260
Immunity, Hypoxia, and Metabolism–the Ménage à Trois of Cancer: Implications for Immunotherapy DOI Open Access
Carla Riera‐Domingo, Annette Audigé, Sara Granja

et al.

Physiological Reviews, Journal Year: 2019, Volume and Issue: 100(1), P. 1 - 102

Published: Aug. 15, 2019

It is generally accepted that metabolism able to shape the immune response. Only recently we are gaining awareness metabolic crosstalk between different tumor compartments strongly contributes harsh microenvironment (TME) and ultimately impairs cell fitness effector functions. The major aims of this review provide an overview on system in cancer; position oxygen shortage competition as ground a restrictive TME important players anti-tumor response; define how immunotherapies affect hypoxia/oxygen delivery landscape tumor; vice versa, metabolites within impinge success immunotherapies. By analyzing preclinical clinical endeavors, will discuss characterization can identify novel targets signatures could be exploited combination with standard help predict benefit new traditional immunotherapeutic drugs.

Language: Английский

Citations

252
Ontogeny of Tumor-Associated Macrophages DOI Creative Commons

Marie Laviron,

Alexandre Boissonnas

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: July 31, 2019

Tumor-associated macrophages (TAM) represent the main immune cell population of tumor microenvironment in most cancer. For decades, TAM have been focus intense investigation to understand how they modulate and their implication therapy failure. One consensus is that are considered exclusively originate from circulating monocyte precursors released bone marrow, fitting original dogma tissue-resident macrophage ontogeny. A second proposed harbor either a classically activated M1 or alternatively M2 polarization profile, with almost opposite anti- pro-tumoral activity respectively. These fundamental pillars now revised face latest discoveries on biology. Embryonic-derived were recently characterized as major contributors pool many tissues. Their turnover derived adult hematopoiesis seems follow regulation at subtissular level. This has shed light an ever more complex diversity than once thought raise question respective development compared classical monocyte-derived macrophages. recent advances highlight actually not fully revealed usefulness deserve be reconsidered. Understanding link between ontogeny various functions growth interaction system represents one future challenges for cancer therapy.

Language: Английский

Citations

205
Investigating immune and non-immune cell interactions in head and neck tumors by single-cell RNA sequencing DOI Creative Commons
Cornelius Kürten, Aditi Kulkarni, Anthony R. Cillo

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Dec. 17, 2021

Head and neck squamous cell carcinoma (HNSCC) is characterized by complex relations between stromal, epithelial, immune cells within the tumor microenvironment (TME). To enable development of more efficacious therapies, we aim to study heterogeneity, signatures unique populations, cell-cell interactions non-immune populations in 6 human papillomavirus (HPV)+ 12 HPV- HNSCC patient matched peripheral blood specimens using single-cell RNA sequencing. Using this dataset 134,606 cells, show type-specific associated with inflammation HPV status, describe negative prognostic value fibroblasts elastic differentiation specifically HPV+ TME, predict therapeutically targetable checkpoint receptor-ligand interactions, that tumor-associated macrophages are dominant contributors PD-L1 other ligands TME. We present a comprehensive view cell-intrinsic mechanisms communication shaping microenvironment.

Language: Английский

Citations

194
Tumor-Derived Retinoic Acid Regulates Intratumoral Monocyte Differentiation to Promote Immune Suppression DOI Creative Commons

Samir Devalaraja,

Tsun Ki Jerrick To,

Ian W. Folkert

et al.

Cell, Journal Year: 2020, Volume and Issue: 180(6), P. 1098 - 1114.e16

Published: March 1, 2020

Language: Английский

Citations

191
Antagonistic Inflammatory Phenotypes Dictate Tumor Fate and Response to Immune Checkpoint Blockade DOI Creative Commons
Eduardo Bonavita, Christian P. Bromley, Gustav Jonsson

et al.

Immunity, Journal Year: 2020, Volume and Issue: 53(6), P. 1215 - 1229.e8

Published: Nov. 20, 2020

Inflammation can support or restrain cancer progression and the response to therapy. Here, we searched for primary regulators of cancer-inhibitory inflammation through deep profiling inflammatory tumor microenvironments (TMEs) linked immune-dependent control in mice. We found that early intratumoral accumulation interferon gamma (IFN-γ)-producing natural killer (NK) cells induced a profound remodeling TME unleashed cytotoxic T cell (CTL)-mediated eradication. Mechanistically, tumor-derived prostaglandin E2 (PGE2) acted selectively on EP2 EP4 receptors NK cells, hampered switch, enabled immune evasion. Analysis patient datasets across human cancers revealed distinct phenotypes resembling those associated with versus escape This allowed us generate gene-expression signature integrated opposing factors predicted survival checkpoint blockade. Our findings identify features milieu establish strategy predict immunotherapy outcomes.

Language: Английский

Citations

182
Analysis of multispectral imaging with the AstroPath platform informs efficacy of PD-1 blockade DOI
Sneha Berry, Nicolás A. Giraldo, Benjamin Green

et al.

Science, Journal Year: 2021, Volume and Issue: 372(6547)

Published: June 10, 2021

Next-generation tissue-based biomarkers for immunotherapy will likely include the simultaneous analysis of multiple cell types and their spatial interactions, as well distinct expression patterns immunoregulatory molecules. Here, we introduce a comprehensive platform multispectral imaging mapping parameters in tumor tissue sections with high-fidelity single-cell resolution. Image data handling components were drawn from field astronomy. Using this "AstroPath" whole-slide only six markers, identified key features pretreatment melanoma specimens that predicted response to anti-programmed death-1 (PD-1)-based therapy, including CD163+PD-L1- myeloid cells CD8+FoxP3+PD-1low/mid T cells. These combined stratify long-term survival after anti-PD-1 blockade. This signature was validated an independent cohort patients different institution.

Language: Английский

Citations

168