Immunosuppressive circuits in tumor microenvironment and their influence on cancer treatment efficacy

Research output: Contribution to journalReview article

3 Citations (Scopus)

Abstract

It has been for long conceived that hallmarks of cancer were intrinsic genetic features driving tumor development, proliferation, and progression, and that targeting such cell-autonomous pathways could be sufficient to achieve therapeutic cancer control. Clinical ex vivo data demonstrated that treatment efficacy often relied on the contribution of host immune responses, hence introducing the concept of tumor microenvironment (TME), namely the existence, along with tumor cells, of non-tumor components that could significantly influence tumor growth and survival. Among the complex network of TME-driving forces, immunity plays a key role and the balance between antitumor and protumor immune responses is a major driver in contrasting or promoting cancer spreading. TME is usually a very immunosuppressed milieu because of a vast array of local alterations contrasting antitumor adaptive immunity, where metabolic changes contribute to cancer dissemination by impairing T cell infiltration and favoring the accrual and activation of regulatory cells. Subcellular structures known as extracellular vesicles then help spreading immunosuppression at systemic levels by distributing genetic and protein tumor repertoire in distant tissues. A major improvement in the knowledge of TME is now pointing the attention back to tumor cells; indeed, recent findings are showing how oncogenic pathways and specific mutations in tumor cells can actually dictate the nature and the function of immune infiltrate. As our information on the reciprocal interactions regulating TME increases, finding a strategy to interfere with TME crosstalk becomes more complex and challenging. Nevertheless, TME interactions represent a promising field for the discovery of novel biomarkers and therapeutic targets for improving treatment efficacy in cancer.

Original languageEnglish
Pages (from-to)407-420
Number of pages14
JournalVirchows Archiv
Volume474
Issue number4
DOIs
Publication statusPublished - Apr 1 2019

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Tumor Microenvironment
Immunosuppressive Agents
Neoplasms
Adaptive Immunity
Immunosuppression
Immunity
Biomarkers
T-Lymphocytes

Keywords

  • Extracellular vesicles
  • Immune checkpoint inhibitors
  • Immunosuppression
  • Metabolic reprogramming
  • Myeloid-derived suppressor cells
  • Oncogenes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

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title = "Immunosuppressive circuits in tumor microenvironment and their influence on cancer treatment efficacy",
abstract = "It has been for long conceived that hallmarks of cancer were intrinsic genetic features driving tumor development, proliferation, and progression, and that targeting such cell-autonomous pathways could be sufficient to achieve therapeutic cancer control. Clinical ex vivo data demonstrated that treatment efficacy often relied on the contribution of host immune responses, hence introducing the concept of tumor microenvironment (TME), namely the existence, along with tumor cells, of non-tumor components that could significantly influence tumor growth and survival. Among the complex network of TME-driving forces, immunity plays a key role and the balance between antitumor and protumor immune responses is a major driver in contrasting or promoting cancer spreading. TME is usually a very immunosuppressed milieu because of a vast array of local alterations contrasting antitumor adaptive immunity, where metabolic changes contribute to cancer dissemination by impairing T cell infiltration and favoring the accrual and activation of regulatory cells. Subcellular structures known as extracellular vesicles then help spreading immunosuppression at systemic levels by distributing genetic and protein tumor repertoire in distant tissues. A major improvement in the knowledge of TME is now pointing the attention back to tumor cells; indeed, recent findings are showing how oncogenic pathways and specific mutations in tumor cells can actually dictate the nature and the function of immune infiltrate. As our information on the reciprocal interactions regulating TME increases, finding a strategy to interfere with TME crosstalk becomes more complex and challenging. Nevertheless, TME interactions represent a promising field for the discovery of novel biomarkers and therapeutic targets for improving treatment efficacy in cancer.",
keywords = "Extracellular vesicles, Immune checkpoint inhibitors, Immunosuppression, Metabolic reprogramming, Myeloid-derived suppressor cells, Oncogenes",
author = "Alessandra Tuccitto and Eriomina Shahaj and Elisabetta Vergani and Simona Ferro and Veronica Huber and Monica Rodolfo and Chiara Castelli and Licia Rivoltini and Viviana Vallacchi",
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T1 - Immunosuppressive circuits in tumor microenvironment and their influence on cancer treatment efficacy

AU - Tuccitto, Alessandra

AU - Shahaj, Eriomina

AU - Vergani, Elisabetta

AU - Ferro, Simona

AU - Huber, Veronica

AU - Rodolfo, Monica

AU - Castelli, Chiara

AU - Rivoltini, Licia

AU - Vallacchi, Viviana

PY - 2019/4/1

Y1 - 2019/4/1

N2 - It has been for long conceived that hallmarks of cancer were intrinsic genetic features driving tumor development, proliferation, and progression, and that targeting such cell-autonomous pathways could be sufficient to achieve therapeutic cancer control. Clinical ex vivo data demonstrated that treatment efficacy often relied on the contribution of host immune responses, hence introducing the concept of tumor microenvironment (TME), namely the existence, along with tumor cells, of non-tumor components that could significantly influence tumor growth and survival. Among the complex network of TME-driving forces, immunity plays a key role and the balance between antitumor and protumor immune responses is a major driver in contrasting or promoting cancer spreading. TME is usually a very immunosuppressed milieu because of a vast array of local alterations contrasting antitumor adaptive immunity, where metabolic changes contribute to cancer dissemination by impairing T cell infiltration and favoring the accrual and activation of regulatory cells. Subcellular structures known as extracellular vesicles then help spreading immunosuppression at systemic levels by distributing genetic and protein tumor repertoire in distant tissues. A major improvement in the knowledge of TME is now pointing the attention back to tumor cells; indeed, recent findings are showing how oncogenic pathways and specific mutations in tumor cells can actually dictate the nature and the function of immune infiltrate. As our information on the reciprocal interactions regulating TME increases, finding a strategy to interfere with TME crosstalk becomes more complex and challenging. Nevertheless, TME interactions represent a promising field for the discovery of novel biomarkers and therapeutic targets for improving treatment efficacy in cancer.

AB - It has been for long conceived that hallmarks of cancer were intrinsic genetic features driving tumor development, proliferation, and progression, and that targeting such cell-autonomous pathways could be sufficient to achieve therapeutic cancer control. Clinical ex vivo data demonstrated that treatment efficacy often relied on the contribution of host immune responses, hence introducing the concept of tumor microenvironment (TME), namely the existence, along with tumor cells, of non-tumor components that could significantly influence tumor growth and survival. Among the complex network of TME-driving forces, immunity plays a key role and the balance between antitumor and protumor immune responses is a major driver in contrasting or promoting cancer spreading. TME is usually a very immunosuppressed milieu because of a vast array of local alterations contrasting antitumor adaptive immunity, where metabolic changes contribute to cancer dissemination by impairing T cell infiltration and favoring the accrual and activation of regulatory cells. Subcellular structures known as extracellular vesicles then help spreading immunosuppression at systemic levels by distributing genetic and protein tumor repertoire in distant tissues. A major improvement in the knowledge of TME is now pointing the attention back to tumor cells; indeed, recent findings are showing how oncogenic pathways and specific mutations in tumor cells can actually dictate the nature and the function of immune infiltrate. As our information on the reciprocal interactions regulating TME increases, finding a strategy to interfere with TME crosstalk becomes more complex and challenging. Nevertheless, TME interactions represent a promising field for the discovery of novel biomarkers and therapeutic targets for improving treatment efficacy in cancer.

KW - Extracellular vesicles

KW - Immune checkpoint inhibitors

KW - Immunosuppression

KW - Metabolic reprogramming

KW - Myeloid-derived suppressor cells

KW - Oncogenes

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U2 - 10.1007/s00428-018-2477-z

DO - 10.1007/s00428-018-2477-z

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VL - 474

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EP - 420

JO - Virchows Archiv - A Pathological Anatomy and Histopathology

JF - Virchows Archiv - A Pathological Anatomy and Histopathology

SN - 0945-6317

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