Immunomodulating and Immunoresistance Properties of Cancer-Initiating Cells: Implications for the Clinical Success of Immunotherapy

Cristina Maccalli, Giorgio Parmiani, Soldano Ferrone

Research output: Contribution to journalReview article

29 Citations (Scopus)

Abstract

Cancer-initiating cells (CICs) represent a relatively rare subpopulation of cells endowed with self-renewal, stemness properties, tumorigenicity in immunodeficient mice, and resistance to standard therapies as well as to immunotherapy. Here, we review the biological and immunological characteristics of CICs with special focus on the immunomodulating mechanisms they utilize to escape from immunosurveillance. The recently developed immunotherapeutic strategies have yielded remarkable clinical results in many types of tumors, indicating that indeed a patient’s immune system can mount an immune response, which is effective in controlling tumor growth. However, a high proportion of patients is resistant or acquires resistance to these therapeutic strategies. The latter findings may reflect, at least in some cases, the inability of the immunotherapeutic strategies used to eradicate CICs. The CICs that escape immune recognition and destruction may give rise to new tumors in the same organ site or through the metastatic colonization in other anatomic sites. Identification of novel therapeutic approaches that can eradicate CICs is a major challenge in the cancer therapy area. An improved understanding of the interactions of CICs with immune system and with tumor microenvironment may contribute to optimize the available therapies and to design novel combination treatments for cancer therapy. Abbreviations: ALDH, aldehyde dehydrogenase; APC, antigen-presenting cells; APM, antigen-processing machinery; CAR: chimeric antigen receptor; CHK1, checkpoint serine/threonine protein kinase; CIC, cancer-initiating cell; CRC, colorectal cancer; CTLA-4, cytotoxic T lymphocyte antigen-4; GBM, glioblastoma multiforme; GDF-15, growth differentiation factor-15; CSPG4: chondroitin sulfate proteoglycan-4; IFN, interferon; IL-4, interleukin-4; IL-10, interleukin-10; IL-13, interleukin-13; IL-13α2, α2 chain of IL-13 receptor; mAb, monoclonal antibody; MDSC, myeloid-derived suppressor cell; MHC, major histocompatibility complex; PD-1, programmed death-1; PD-L1 programmed death ligand-1; PDK, 3-phosphoinositide-dependent protein kinase-1; PGE2, prostaglandin E2; STAT3, signal transducer and activator of transcription 3; TGFB-1, transforming growth factor beta-1; Treg, T regulatory cell.

Original languageEnglish
Pages (from-to)221-238
Number of pages18
JournalImmunological Investigations
Volume46
Issue number3
DOIs
Publication statusPublished - 3 Apr 2017

Fingerprint

Immunotherapy
Neoplasms
Growth Differentiation Factor 15
Interleukin-13
Dinoprostone
Interleukin-4
Interleukin-10
Therapeutics
Immune System
3-Phosphoinositide-Dependent Protein Kinases
Interleukin-13 Receptors
CTLA-4 Antigen
Immunologic Monitoring
STAT3 Transcription Factor
Aldehyde Dehydrogenase
Antigen Receptors
Tumor Microenvironment
Protein-Serine-Threonine Kinases
Antigen Presentation
Antigen-Presenting Cells

Keywords

  • Cancer-initiating cell markers
  • cancer-initiating cells
  • chimeric antigen receptor (CAR) T cells
  • immune checkpoint molecules
  • immunological profile
  • immunosuppressive properties
  • immunotherapy
  • neo-epitopes
  • T-cell responses

ASJC Scopus subject areas

  • Immunology

Cite this

Immunomodulating and Immunoresistance Properties of Cancer-Initiating Cells : Implications for the Clinical Success of Immunotherapy. / Maccalli, Cristina; Parmiani, Giorgio; Ferrone, Soldano.

In: Immunological Investigations, Vol. 46, No. 3, 03.04.2017, p. 221-238.

Research output: Contribution to journalReview article

@article{9b119ee29a3a472c9b11d649395fbe5e,
title = "Immunomodulating and Immunoresistance Properties of Cancer-Initiating Cells: Implications for the Clinical Success of Immunotherapy",
abstract = "Cancer-initiating cells (CICs) represent a relatively rare subpopulation of cells endowed with self-renewal, stemness properties, tumorigenicity in immunodeficient mice, and resistance to standard therapies as well as to immunotherapy. Here, we review the biological and immunological characteristics of CICs with special focus on the immunomodulating mechanisms they utilize to escape from immunosurveillance. The recently developed immunotherapeutic strategies have yielded remarkable clinical results in many types of tumors, indicating that indeed a patient’s immune system can mount an immune response, which is effective in controlling tumor growth. However, a high proportion of patients is resistant or acquires resistance to these therapeutic strategies. The latter findings may reflect, at least in some cases, the inability of the immunotherapeutic strategies used to eradicate CICs. The CICs that escape immune recognition and destruction may give rise to new tumors in the same organ site or through the metastatic colonization in other anatomic sites. Identification of novel therapeutic approaches that can eradicate CICs is a major challenge in the cancer therapy area. An improved understanding of the interactions of CICs with immune system and with tumor microenvironment may contribute to optimize the available therapies and to design novel combination treatments for cancer therapy. Abbreviations: ALDH, aldehyde dehydrogenase; APC, antigen-presenting cells; APM, antigen-processing machinery; CAR: chimeric antigen receptor; CHK1, checkpoint serine/threonine protein kinase; CIC, cancer-initiating cell; CRC, colorectal cancer; CTLA-4, cytotoxic T lymphocyte antigen-4; GBM, glioblastoma multiforme; GDF-15, growth differentiation factor-15; CSPG4: chondroitin sulfate proteoglycan-4; IFN, interferon; IL-4, interleukin-4; IL-10, interleukin-10; IL-13, interleukin-13; IL-13α2, α2 chain of IL-13 receptor; mAb, monoclonal antibody; MDSC, myeloid-derived suppressor cell; MHC, major histocompatibility complex; PD-1, programmed death-1; PD-L1 programmed death ligand-1; PDK, 3-phosphoinositide-dependent protein kinase-1; PGE2, prostaglandin E2; STAT3, signal transducer and activator of transcription 3; TGFB-1, transforming growth factor beta-1; Treg, T regulatory cell.",
keywords = "Cancer-initiating cell markers, cancer-initiating cells, chimeric antigen receptor (CAR) T cells, immune checkpoint molecules, immunological profile, immunosuppressive properties, immunotherapy, neo-epitopes, T-cell responses",
author = "Cristina Maccalli and Giorgio Parmiani and Soldano Ferrone",
year = "2017",
month = "4",
day = "3",
doi = "10.1080/08820139.2017.1280051",
language = "English",
volume = "46",
pages = "221--238",
journal = "Immunological Investigations",
issn = "0882-0139",
publisher = "Informa Healthcare",
number = "3",

}

TY - JOUR

T1 - Immunomodulating and Immunoresistance Properties of Cancer-Initiating Cells

T2 - Implications for the Clinical Success of Immunotherapy

AU - Maccalli, Cristina

AU - Parmiani, Giorgio

AU - Ferrone, Soldano

PY - 2017/4/3

Y1 - 2017/4/3

N2 - Cancer-initiating cells (CICs) represent a relatively rare subpopulation of cells endowed with self-renewal, stemness properties, tumorigenicity in immunodeficient mice, and resistance to standard therapies as well as to immunotherapy. Here, we review the biological and immunological characteristics of CICs with special focus on the immunomodulating mechanisms they utilize to escape from immunosurveillance. The recently developed immunotherapeutic strategies have yielded remarkable clinical results in many types of tumors, indicating that indeed a patient’s immune system can mount an immune response, which is effective in controlling tumor growth. However, a high proportion of patients is resistant or acquires resistance to these therapeutic strategies. The latter findings may reflect, at least in some cases, the inability of the immunotherapeutic strategies used to eradicate CICs. The CICs that escape immune recognition and destruction may give rise to new tumors in the same organ site or through the metastatic colonization in other anatomic sites. Identification of novel therapeutic approaches that can eradicate CICs is a major challenge in the cancer therapy area. An improved understanding of the interactions of CICs with immune system and with tumor microenvironment may contribute to optimize the available therapies and to design novel combination treatments for cancer therapy. Abbreviations: ALDH, aldehyde dehydrogenase; APC, antigen-presenting cells; APM, antigen-processing machinery; CAR: chimeric antigen receptor; CHK1, checkpoint serine/threonine protein kinase; CIC, cancer-initiating cell; CRC, colorectal cancer; CTLA-4, cytotoxic T lymphocyte antigen-4; GBM, glioblastoma multiforme; GDF-15, growth differentiation factor-15; CSPG4: chondroitin sulfate proteoglycan-4; IFN, interferon; IL-4, interleukin-4; IL-10, interleukin-10; IL-13, interleukin-13; IL-13α2, α2 chain of IL-13 receptor; mAb, monoclonal antibody; MDSC, myeloid-derived suppressor cell; MHC, major histocompatibility complex; PD-1, programmed death-1; PD-L1 programmed death ligand-1; PDK, 3-phosphoinositide-dependent protein kinase-1; PGE2, prostaglandin E2; STAT3, signal transducer and activator of transcription 3; TGFB-1, transforming growth factor beta-1; Treg, T regulatory cell.

AB - Cancer-initiating cells (CICs) represent a relatively rare subpopulation of cells endowed with self-renewal, stemness properties, tumorigenicity in immunodeficient mice, and resistance to standard therapies as well as to immunotherapy. Here, we review the biological and immunological characteristics of CICs with special focus on the immunomodulating mechanisms they utilize to escape from immunosurveillance. The recently developed immunotherapeutic strategies have yielded remarkable clinical results in many types of tumors, indicating that indeed a patient’s immune system can mount an immune response, which is effective in controlling tumor growth. However, a high proportion of patients is resistant or acquires resistance to these therapeutic strategies. The latter findings may reflect, at least in some cases, the inability of the immunotherapeutic strategies used to eradicate CICs. The CICs that escape immune recognition and destruction may give rise to new tumors in the same organ site or through the metastatic colonization in other anatomic sites. Identification of novel therapeutic approaches that can eradicate CICs is a major challenge in the cancer therapy area. An improved understanding of the interactions of CICs with immune system and with tumor microenvironment may contribute to optimize the available therapies and to design novel combination treatments for cancer therapy. Abbreviations: ALDH, aldehyde dehydrogenase; APC, antigen-presenting cells; APM, antigen-processing machinery; CAR: chimeric antigen receptor; CHK1, checkpoint serine/threonine protein kinase; CIC, cancer-initiating cell; CRC, colorectal cancer; CTLA-4, cytotoxic T lymphocyte antigen-4; GBM, glioblastoma multiforme; GDF-15, growth differentiation factor-15; CSPG4: chondroitin sulfate proteoglycan-4; IFN, interferon; IL-4, interleukin-4; IL-10, interleukin-10; IL-13, interleukin-13; IL-13α2, α2 chain of IL-13 receptor; mAb, monoclonal antibody; MDSC, myeloid-derived suppressor cell; MHC, major histocompatibility complex; PD-1, programmed death-1; PD-L1 programmed death ligand-1; PDK, 3-phosphoinositide-dependent protein kinase-1; PGE2, prostaglandin E2; STAT3, signal transducer and activator of transcription 3; TGFB-1, transforming growth factor beta-1; Treg, T regulatory cell.

KW - Cancer-initiating cell markers

KW - cancer-initiating cells

KW - chimeric antigen receptor (CAR) T cells

KW - immune checkpoint molecules

KW - immunological profile

KW - immunosuppressive properties

KW - immunotherapy

KW - neo-epitopes

KW - T-cell responses

UR - http://www.scopus.com/inward/record.url?scp=85016075617&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016075617&partnerID=8YFLogxK

U2 - 10.1080/08820139.2017.1280051

DO - 10.1080/08820139.2017.1280051

M3 - Review article

C2 - 28287848

AN - SCOPUS:85016075617

VL - 46

SP - 221

EP - 238

JO - Immunological Investigations

JF - Immunological Investigations

SN - 0882-0139

IS - 3

ER -