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Novel Methods to Overcome Acquired Resistance to Immunotherapy

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Current Applications for Overcoming Resistance to Targeted Therapies

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 20))

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Abstract

The remarkable success of immunotherapy, including immune checkpoint blockade therapy (ICBT) in clinical settings, such as in melanoma patients and patients with DNA mismatch repair deficient tumors, has shifted the paradigm of cancer treatment. However, immunotherapy continues to face major challenges in controlling malignancy due to both intrinsic and acquired resistance mechanisms. Here, we discuss the mechanisms by which cancer immunotherapy has harnessed the immune system to target tumor progression, as well as the mechanisms of acquired resistance to immunotherapy. We also describe novel approaches in overcoming this resistance, with a particular focus on ICBT. We explore mechanisms by which tumor-intrinsic cues, tumor microenvironmental factors, and the host microbiome might impact the efficacy and resistance often seen during ICBT. Furthermore, we introduce technologies that will identify biomarkers from mouse and human models to predict clinical benefits for ICBT in cancer patients and promising emerging strategies to overcome ICBT resistance.

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Abbreviations

β2m:

Beta-2-microglobulin

A2AR:

Adenosine receptor

ADCC:

Antibody-dependent cell-mediated cytotoxicity

AKT:

Protein kinase B

APC:

Antigen-presenting cell

AXL:

Tyrosine-protein kinase receptor UFO

BATTLE-1:

Biomarker-integrated approaches of targeted therapy for lung cancer elimination

BCG:

Bacille Calmette-Guérin

CAF:

Cancer-associated fibroblast

CAR:

Chimeric antigen receptor

CDK:

Cyclin-dependent kinase

CK2:

Casein kinase 2

CT:

Computed tomography

ctDNA:

Circulating tumor DNA

CTLA-4:

Cytotoxic T-lymphocyte antigen 4

CTLs:

Cytotoxic T-cells

DAMPs:

Danger-associated molecular patterns

DC:

Dendritic cell

Eomes:

Eomesodermin

ERK:

Extracellular signal–regulated kinases

FAP:

Fibroblast activation protein

Fas:

Tumor necrosis factor receptor superfamily, member 6

FasL:

Fas ligand

FDA:

Food and Drug Administration

GADS:

GRB2-related adaptor downstream of Shc

GEM:

Genetically engineered mouse

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

GRB2:

Growth factor receptor-bound protein 2

HMGB1:

High-mobility group box 1

ICBT:

Immune checkpoint blockade therapy

ICOS:

Inducible T-cell co-stimulator

IDO:

Indoleamine 2,3-dioxygenase

IFNGR:

Interferon-gamma receptor

IFN-α:

Interferon-alpha

IFN-γ:

Interferon-gamma

IL-2:

Interleukin-2

IL-4:

Interleukin-4

IRF:

Tripartite motif containing 63

JAK:

Janus kinases

KIR:

Killer cell immunoglobulin-like receptors

LAG-3:

Lymphocyte activation gene 3

LCK:

Lymphocyte-specific protein tyrosine kinase

LCMV:

Lymphocytic choriomeningitis virus

LOXL2:

Lysyl oxidase-like 2

MDSC:

Myeloid-derived suppressor cell

MHC:

Major histocompatibility complex

NCR:

Natural cytotoxicity receptors

NK:

Natural killer (cell)

PD-1:

Programmed death 1

PD-L1:

Programmed death-ligand 1

PD-L2:

Programmed death-ligand 2

PI3K:

Phosphoinositide 3-kinase

PIAS4:

Protein inhibitor of activated STAT 4

PIP3:

Phosphatidylinositol (3,4,5)-trisphosphate

PKC:

Protein kinase C

PROSPECT:

Profiling of resistance patterns and oncogenic signaling pathways in evaluation of cancers of the thorax

PTEN:

Phosphatase and tensin homolog

RAR:

Retinoic acid receptor

RECIST:

Response evaluation criteria in solid tumors

ROR2:

Receptor tyrosine kinase-like orphan receptor 2

SCF:

Skp, Cullin, F-box containing complex

SHP-1:

Tyrosine-protein phosphatase non-receptor type 6

SHP-2:

Tyrosine-protein phosphatase non-receptor type 11

SMAD3:

Mothers against decapentaplegic homolog 3

SOCS1:

Suppressor of cytokine signaling 1

SOX3:

SRY-box 3

TAGLN:

Transgelin

T-bet:

T-box transcription factor 21

TCGA:

The Cancer Genome Atlas

TCR:

T-cell receptors

TGF-β:

Transforming growth factor-beta

TIM-3:

T-cell immunoglobulin and mucin domain 3

TME:

Tumor microenvironment

TNF:

Tumor necrosis factor

Tregs:

Regulatory T-cells

TWIST2:

Twist-related protein 2

VEGF:

Vascular endothelial growth factor

VISTA:

V-domain immunoglobulin suppressor of T-cell activation

WHO:

World Health Organization

WNT5A:

Wingless-type MMTV integration site family, member 5A

ZAP70:

Zeta-chain-associated protein kinase 70

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Author notes

  1. Ce Yuan, John Markus Rieth, and Dechen Wangmo contributed equally to this work.

Authors and Affiliations

  1. Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA

    Xianda Zhao, Ce Yuan, Dechen Wangmo & Subbaya Subramanian

  2. Department of Internal Medicine, Carver College of Medicine, Iowa City, IA, USA

    John Markus Rieth

  3. Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA

    Subbaya Subramanian

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  1. Xianda Zhao
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Correspondence to Subbaya Subramanian .

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  1. Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, Canada

    Myron R. Szewczuk

  2. Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, Canada

    Bessi Qorri

  3. Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, Canada

    Manpreet Sambi

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Zhao, X., Yuan, C., Rieth, J.M., Wangmo, D., Subramanian, S. (2019). Novel Methods to Overcome Acquired Resistance to Immunotherapy. In: Szewczuk, M., Qorri, B., Sambi, M. (eds) Current Applications for Overcoming Resistance to Targeted Therapies. Resistance to Targeted Anti-Cancer Therapeutics, vol 20. Springer, Cham. https://doi.org/10.1007/978-3-030-21477-7_4

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