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 language | English |
|---|---|
| Pages (from-to) | 407-420 |
| Number of pages | 14 |
| Journal | Virchows Archiv |
| Volume | 474 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 1 2019 |
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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
Immunosuppressive circuits in tumor microenvironment and their influence on cancer treatment efficacy. / Tuccitto, Alessandra; Shahaj, Eriomina; Vergani, Elisabetta; Ferro, Simona; Huber, Veronica; Rodolfo, Monica; Castelli, Chiara; Rivoltini, Licia; Vallacchi, Viviana.
In: Virchows Archiv, Vol. 474, No. 4, 01.04.2019, p. 407-420.Research output: Contribution to journal › Review article
}
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=85055982699&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055982699&partnerID=8YFLogxK
U2 - 10.1007/s00428-018-2477-z
DO - 10.1007/s00428-018-2477-z
M3 - Review article
C2 - 30374798
AN - SCOPUS:85055982699
VL - 474
SP - 407
EP - 420
JO - Virchows Archiv - A Pathological Anatomy and Histopathology
JF - Virchows Archiv - A Pathological Anatomy and Histopathology
SN - 0945-6317
IS - 4
ER -