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Resistance of Cancer Cells to CTL-Mediated Immunotherapy pp 159–174Cite as

Evasion of Cytotoxic Lymphocyte and Pulmonary Macrophage-Mediated Immune Responses in Lung Cancer

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

Abstract

Lung cancer is responsible for more cancer-related deaths than colon, breast and prostate cancers combined. Survival rates for lung cancer are generally lower than those for most cancers, with an overall 5-year survival rate for lung cancer of about 16 % compared to 65 % for colon cancer, 89 % for breast cancer, and over 99 % for prostate cancer. Lung cancer comprises several types with varying response to therapy and survival rates; although they can be broadly grouped into small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). NSCLC includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. SCLC accounts for approximately 20 % of all primary lung cancers and in general and tends to be more aggressive; some studies suggest that 60–70 % of patients with small cell lung cancer have evidence of distant spread at the time of initial diagnosis; treatment usually is limited to chemotherapy and/or radiation therapy. By contrast, surgical resection for NSLC may be an option.

COPD/emphysema is a highly prevalent airways disease that arises as a result of noxious injury to the lungs. Cigarette smoke plays a significant role in the aetiology of both COPD and lung cancer. Both smokers and COPD patients have an increased risk of developing lung cancer; however, there is an increased risk of developing lung cancer in smokers with COPD far above that of smokers without COPD. The carcinogenic effects of tobacco smoke have been well-described with over 80 % of lung cancer cases occurring in smokers or ex-smokers. The burden of COPD and the associated prevalence of COPD-associated lung cancer are projected to increase in the coming decades due to continued exposure to COPD risk factors and the changing age structure of the world’s population. Despite these alarming statistics, it is unknown why many lung cancers are relatively resistant to conventional therapies.

The authors have no potential conflicts of interest to disclose.

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Abbreviations

AA:

Arachidonic acid

COPD:

Chronic obstructive pulmonary disease

COX:

Cyclooxygenase-2

CTL:

Cytotoxic T-cells

EP1–4:

E-prostanoid 2 receptor 1–4

IFN:

Interferon

IL-:

Interleukin

LC-ESI-MSMS:

High performance liquid chromatography—electrospray tandem mass spectrometry

NK cells:

Natural killer cells

NSCLC:

Non small cell lung cancer

PGE2:

Eicosanoid prostaglandin E2

PI-9:

Proteinase inhibitor 9

SCLC:

Small cell lung cancer

TGF:

Transforming growth factor

TNF:

Tumour necrosis factor

Tregs:

Regulatory T lymphocytes

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Acknowledgements

The authors acknowledge the expert contributions by Jessica Ahern, Geoffrey Matthews, Cyd Soriano, Frances Dehle, Paul N Reynolds, Hubertus Jersmann and Mark Holmes.

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Authors and Affiliations

  1. Department of Lung Research, Hanson Institute; Thoracic Medicine, Royal Adelaide Hospital, and Medicine, University of Adelaide, Adelaide, South Australia

    Sandra Hodge & Greg Hodge

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  1. Sandra Hodge
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Correspondence to Sandra Hodge .

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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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Hodge, S., Hodge, G. (2015). Evasion of Cytotoxic Lymphocyte and Pulmonary Macrophage-Mediated Immune Responses in Lung Cancer. 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_8

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