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Resistance of Cancer Cells to CTL-Mediated Immunotherapy pp 303–349Cite as

Quality of CTL Therapies: A Changing Landscape

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Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 7))

Abstract

The identification and cloning of tumor-associated antigens (TAA) has led to clinical trials using vaccines designed to boost the host anti-tumor immune response. Impressive clinical responses have also been documented in melanoma patients treated with these tumor-reactive T cells. These studies and others indicate the potential of T cells for their use in the adoptive therapy of cancer. However, technical issues related to the generation of a large number of tumor-specific T cells have significantly restricted the use of this promising approach. Moreover, only limited success has been achieved in terms of tumor regression or patient survival in numerous other immunotherapy trials. Evidences suggest that various tumor-escape strategies such as defects in antigen presentation, tumor-induced immunosuppression, induction of T-cell death, T-cell receptor dysfunction, the presence of tolerogenic dendritic cells and regulatory T cells undermine the effectiveness of adoptively transferred T cells. Thus, a better understanding for eliciting effective anti-tumor immunity that leads to cancer regression in all patients is needed. Herein, we discuss the recent developments aimed at overcoming the constraints that exist and are changing the landscape for effectively employing adoptive T cell therapy to treat cancer.

Conflict of interest: The authors declare no conflict of interest.

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Abbreviations

2-DG:

2-Deoxy-d-glucose

ACT:

Adoptive cell therapy

AG:

Antigen

AICD:

Activation induced cell death

AMPK:

Adenosine monophosphate-activated protein kinase

APC:

Antigen presenting cell

BiTE:

Bi-specific antibody T cell engager

BTLA-4:

B and T lymphocyte attenuator 4

cAMP:

Cyclic AMP

CAR:

Chimeric antigen receptors

CMV:

Cytomegalovirus

COX-2:

Cyclooxygenase-2

c-SH:

Cell surface thiols

CTL:

Cytotoxic T lymphocyte

CTLA-4:

Cytotoxic T-lymphocyte-associated protein 4

DC:

Dendritic cells

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GITR:

Glucocorticoid-induced TNFR family related gene

GLUT-1:

Glucose transporter 1

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

GzmB:

Granzyme B

HAART:

Highly active antiretroviral therapy

HIF-1α:

Hypoxia-inducible factor 1-alpha

HIV:

Human immunodeficiency virus

HLA:

Human lymphocyte antigen

ICOS:

Inducible T-cell costimulator

IFNγ:

Interferon gamma

iGSH:

Intracellular glutathione

IL:

Interleukin

iNOS:

Inducible nitric oxide synthase

KO:

Knockout

LAG-3:

Lymphocyte-activation gene 3

MDSC:

Myeloid-derived suppressor cell

MHC:

Major histocompatibility complex

miRNA:

MicroRNA

mTOR:

Mammalian target of rapamycin

NKT:

Natural killer T cells

NO:

Nitric oxide

PBL:

Peripheral blood lymphocytes

PD-1:

Programmed death receptor-1

PGE2:

Prostaglandin E2

RIPK:

Receptor interacting kinases

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

TAA:

Tumor associated antigens

TAM:

Tumor-associated macrophages

TCA:

Tricarboxylic acid

TCM :

T central memory

TCR:

T cell receptor

Teff:

T effector cell

TEM :

T effector memory

TGFβ:

Transforming growth factor beta

TIL:

Tumor infiltrating lymphocytes

TIM-3:

T cell immunoglobulin mucin-3

TNFα:

Tumor necrosis factor alpha

Treg:

T regulatory cell

TSCM :

T memory stem cells

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Acknowledgement

Authors acknowledge help from Dr. Radhika Gudi at MUSC for critical reading of this manuscript and help in preparing this manuscript. We also apologize to our colleagues for not citing all primary research articles owing to space restrictions. This work was supported in part by funds from the Department of Surgery (MUSC) and NIH R01CA138930, R01AR057643 and PO1 CA154778.

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Authors and Affiliations

  1. Department of Surgery, Hollings Cancer Center (HO 512H), Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC, 29425, USA

    Krishnamurthy Thyagarajan, Shilpak Chatterjee, Pravin Kesarwani & Shikhar Mehrotra

  2. Department of Surgery, Loyola University, Maywood, IL, 60153, USA

    Michael I. Nishimura

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  1. Krishnamurthy Thyagarajan
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  2. Shilpak Chatterjee
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  3. Pravin Kesarwani
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  4. Michael I. Nishimura
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  5. Shikhar Mehrotra
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Correspondence to Shikhar Mehrotra .

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Editors and Affiliations

  1. Department of Microbiology, Immunology a, University of California at Los Angeles,, Los Angeles, California, USA

    Benjamin Bonavida

  2. Institut Gustave Roussy, Villejuif, France

    Salem Chouaib

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Thyagarajan, K., Chatterjee, S., Kesarwani, P., Nishimura, M.I., Mehrotra, S. (2015). Quality of CTL Therapies: A Changing Landscape. In: Bonavida, B., Chouaib, S. (eds) Resistance of Cancer Cells to CTL-Mediated Immunotherapy. Resistance to Targeted Anti-Cancer Therapeutics, vol 7. Springer, Cham. https://doi.org/10.1007/978-3-319-17807-3_14

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