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The Immune Response to Non-Small Cell Lung Cancer

By Chandra Ohri

Abstract

Non-small cell lung cancer (NSCLC) is responsible for more deaths worldwide than any other cancer. Currently, 5-year survival for patients with stage IA disease is just 67%. Chemotherapy offers no cure at present for patients with NSCLC. It is now recognised that the immune system plays a significant role in both tumour modulation and progression. Therefore, a better understanding of immune responses to NSCLC may lead to the development of novel therapies. \ud In these studies, I have investigated, using immunohistochemistry, the microlocalisation of macrophage and mast cell phenotypes (as well as mast cell degranulation), TNFα expression, non-macrophage expression of markers associated with macrophage phenotypes, chemokine receptors and markers of apoptosis and cellular proliferation in surgically resected NSCLC tissue. \ud These studies have demonstrated for the first time in NSCLC that there are two major macrophage phenotypes, M1 and M2, and that the cytotoxic M1 phenotype predominates in the islets of patients with extended survival. The presence of high numbers of mast cells in the islets, irrespective of phenotype, also predicts extended survival. In addition, TNFα expression in tumour islets was found to be an independent predictor of increased survival but its expression in tumour stroma was an independent predictor of poor survival. Also, patients with increased tumour islet expression of markers associated with cytotoxic macrophages (HLA-DR, iNOS, MRP 8/14 and TNFα) by non-macrophage cells was associated with extended survival. Patients with increased expression of CXCR3 and CCR1 in their tumour islets also had extended survival suggesting that these chemokine receptors may be involved in a pathway attracting cytotoxic components of the immune system into tumour islets. \ud In summary, these studies highlight the importance of microlocalisation and phenotype of immune cells in determining whether they play a pro- or anti-tumorigenic role in NSCLC

Publisher: University of Leicester
Year: 2010
OAI identifier: oai:lra.le.ac.uk:2381/8195

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  1. (2008). A clinical study assessing the tolerability and biological effects of infliximab, a TNF-alpha inhibitor, in patients with advanced cancer",
  2. (2000). A Comparison of Human S100A12 with MRP-14 (S100A9)",
  3. (2007). A cytokine-mediated link between innate immunity, inflammation, and cancer",
  4. (2000). A high number of tumor-infiltrating lymphocytes are associated with a small tumor size, low tumor stage, and a favorable prognosis in operated small cell lung carcinoma",
  5. (1986). A monoclonal antibody to a subset of human monocytes found only in the peripheral blood and inflammatory tissues",
  6. (2002). A novel phenotype for an activated macrophage: the type 2 activated macrophage",
  7. (1998). Activated T lymphocytes induce degranulation and cytokine production by human mast cells following cell-to-cell contact",
  8. (1995). Activation of gamma delta T cells for production of IFN-gamma is mediated by bacteria via macrophage-derived cytokines IL-1 and IL-12",
  9. (2005). Activation of Tumor-Associated Macrophages by the Vascular Disrupting Agent 5,6-Dimethylxanthenone-4-Acetic Acid Induces an Effective CD8+ T-CellMediated Antitumor Immune Response in Murine Models of Lung Cancer and Mesothelioma",
  10. (2003). Adalimumab, a fully human anti tumor necrosis factor-alpha monoclonal antibody, and concomitant standard antirheumatic therapy for the treatment of rheumatoid arthritis: results of STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis)",
  11. (2005). Adipose tissue, adipokines, and inflammation",
  12. (2005). Alcohol and pancreatic cancer",
  13. (2003). Alternative activation of macrophages",
  14. (2005). Angiogenesis as a therapeutic target",
  15. (2006). Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials",
  16. (1994). Apoptosis. Its significance in cancer and cancer therapy",
  17. (2004). Assessment of apoptosis by M30 immunoreactivity and the correlation with morphological criteria in normal colorectal mucosa, adenomas and carcinomas",
  18. (2004). Association of macrophages, mast cells and eosinophil leukocytes with angiogenesis and tumor stage in non-small cell lung carcinomas (NSCLC)",
  19. (2006). Association of TNF-alpha polymorphism with susceptibility to and severity of non-small cell lung cancer",
  20. (2002). Bacterial strategies for overcoming host innate and adaptive immune responses",
  21. (1999). Bone marrow angiogenesis and mast cell density increase simultaneously with progression of human multiple myeloma",
  22. (1993). Bronchogenic carcinoma: immunologic aspects",
  23. (2004). Cancer and the chemokine network",
  24. (2009). Cancer diagnosis in first-degree relatives and non-small cell lung cancer risk: Results from a multi-centre case-control study in Europe",
  25. (2006). Cancer Statistics,
  26. (2008). Cancer-related inflammation",
  27. (1957). Cancer: a biological approach. III. Viruses associated with neoplastic conditions. IV. Practical applications",
  28. (2004). Cancer: an inflammatory link",
  29. (2006). CD163 positive subsets of blood dendritic cells: the scavenging macrophage receptors CD163 and CD91 are coexpressed on human dendritic cells and monocytes",
  30. (2007). CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages",
  31. (1984). Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67",
  32. (1998). Cell suicide for beginners",
  33. (2006). Characterisation of dendritic cell subsets in lung cancer micro-environments",
  34. (2008). Chemokine CXCL13 is overexpressed in the tumour tissue and in the peripheral blood of breast cancer patients",
  35. (1999). Chemokines and chemokine receptors in infectious diseases",
  36. (2002). Chemotherapy for Advanced Non-Small-Cell Lung Cancer: Who, What, When, Why?",
  37. (2004). Chemotherapy versus supportive care in advanced non-small cell lung cancer: improved survival without detriment to quality of life",
  38. (2001). Chronic immune activation and inflammation as the cause of malignancy",
  39. (2002). Chronic inflammation and cancer",
  40. (2003). Chymase-positive mast cells in small sized adenocarcinoma of the lung",
  41. (1998). Clinical applications of TNF[alpha] in cancer",
  42. (2002). Clinical effects of tumor-associated macrophages and dendritic cells on renal cell carcinoma",
  43. (2004). Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial",
  44. (1999). Combined modality therapy of nonsmall cell lung cancers",
  45. (2004). Correlation of Histological Localization of Tumorassociated Macrophages with Clinicopathological Features in Endometrial Cancer",
  46. (2003). Current Developments in Cancer Vaccines and Cellular Immunotherapy",
  47. (2006). Cutting Edge: CD28 Controls Dominant Regulatory T Cell Activity during Active Immunization",
  48. (2002). Decoding the Patterns of Self and Nonself by the Innate Immune System",
  49. (1977). Defense mechanisms of the respiratory membrane",
  50. (2005). Delays in the diagnosis of six cancers: analysis of data from
  51. (1998). Dendritic cells and the control of immunity",
  52. (2004). Depletion of CXCR2 inhibits tumor growth and angiogenesis in a murine model of lung cancer",
  53. (2005). Detection of epithelial cell death in the body by cytokeratin 18 measurement",
  54. (1998). Different patterns of stromal and cancer cell thymidine phosphorylase reactivity in nonsmall-cell lung cancer: impact on tumour neoangiogenesis and survival",
  55. (1996). Differential regulation of interleukin-12- and interleukin-15-induced natural killer cell activation by interleukin-4",
  56. (2001). Discovery of a Novel Member of the Histamine Receptor Family",
  57. (2006). Distinct role of macrophages in different tumor microenvironments",
  58. (1993). Effect of late administration of anti-TNF alpha antibodies on a Salmonella infection in the mouse model",
  59. (2004). Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed",
  60. (2006). Efficiency of recombinant human TNF in human cancer therapy",
  61. (1988). Endogenous tumor necrosis factor (cachectin) is essential to host resistance against Listeria monocytogenes infection",
  62. (2001). Epidermal Growth Factor Receptor and HER2-neu mRNA Expression in Non-Small Cell Lung Cancer Is Correlated with Survival",
  63. (2003). Epidermal growth factor receptors and cyclooxygenase-2 in the pathogenesis of non-small cell lung cancer: potential targets for chemoprevention and systemic therapy",
  64. (2008). Epstein-Barr virus-associated epithelial and mesenchymal neoplasms",
  65. (2005). Erlotinib in lung cancer - molecular and clinical predictors of outcome",
  66. (2003). EUROCARE-3: survival of cancer patients diagnosed 1990-94--results and commentary",
  67. (1998). Expression of CEA and trophoblastic cell markers by lung carcinoma in association with histological characteristics and serum marker levels",
  68. (2001). Expression of HLA-DR is reduced in tumor infiltrating immune cells (TIICs) and regional lymph nodes of non-small-cell lung carcinomas. A putative mechanism of tumor-induced immunosuppression?",
  69. (2009). First- and second-line therapy for advanced nonsmall cell lung cancer",
  70. (2008). Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial",
  71. (2005). Global cancer statistics,
  72. (1991). Growth factors in development, transformation, and tumorigenesis",
  73. (2009). Helicobacter pylori and gastric carcinogenesis",
  74. (1997). Hepatitis B Virus Infection", The New England
  75. (1995). Heterodimers of the calciumbinding proteins MRP8 and MRP14 are expressed on the surface of human monocytes upon adherence to fibronectin and collagen. Relation to TNF-alpha, IL-6, and superoxide production",
  76. (1995). Heterogeneity of human mast cells based on cytokine content",
  77. (2003). High expression of nitric oxide synthases is a favorable prognostic sign in non-small cell lung carcinoma",
  78. (2008). High tumour islet macrophage infiltration correlates with improved patient survival but not with EGFR mutations, gene copy number or protein expression in resected non-small cell lung cancer",
  79. (2005). Histamine and histidine decarboxylase upregulation in colorectal cancer: correlation with tumor stage",
  80. (2007). Host epigenetic modifications by oncogenic viruses",
  81. (2006). Human NK cell education by inhibitory receptors for MHC class I",
  82. (2007). Hyperactive Ras in developmental disorders and cancer",
  83. (2007). Hypoxic Regulation of Glucose Transport, Anaerobic Metabolism and Angiogenesis in Cancer: Novel Pathways and Targets for Anticancer Therapeutics",
  84. (2000). Immune cell infiltrates and prognosis in primary carcinoma of the lung",
  85. (2000). Immune deviation and Fas-mediated deletion limit antitumor activity after multiple dendritic cell vaccinations in mice",
  86. (1987). Immunoregulatory activity of recombinant human tumor necrosis factor (TNF)-alpha: induction of TNF receptors on human T cells and TNF-alpha- mediated enhancement of T cell responses",
  87. (1998). Immunoregulatory roles of IL-10 in innate immunity: IL-10 inhibits macrophage production of IFN-gamma-inducing factors but enhances NK cell production of IFN-gamma",
  88. (2007). Immunosuppressive Strategies that are Mediated by Tumor Cells",
  89. (2008). Immunotherapy for lung cancer",
  90. (2008). Immunotherapy of autoimmunity and cancer: the penalty for success",
  91. (2008). Induction of Immune Responses and Clinical Efficacy in a Phase II Trial of IDM-2101, a 10-Epitope Cytotoxic TLymphocyte Vaccine, in Metastatic Non-Small-Cell Lung Cancer",
  92. (1997). Infiltration of lung carcinomas with macrophages of the 27E10-positive phenotype",
  93. (1997). Infiltration of mononuclear inflammatory cells into primary colorectal carcinomas: an immunohistological analysis",
  94. (2001). Inflammation and cancer: back to Virchow?",
  95. (2002). Inflammation and cancer",
  96. (2007). Inflammation, atrophy, and gastric cancer",
  97. (2009). Inflammatory bowel disease: a model of chronic inflammation-induced cancer",
  98. (2004). Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adenocarcinoma",
  99. (1999). Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis",
  100. (2000). Infliximab and Methotrexate in the Treatment of Rheumatoid Arthritis", The New England
  101. (1994). Inhibition of interleukin 8 attenuates angiogenesis in bronchogenic carcinoma",
  102. (2008). Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica",
  103. (2000). Innate Immunity", The New England
  104. (2004). Integration of Toll-like receptor and phagocytic signaling for tailored immunity",
  105. (2000). Interleukin-8 Messenger Ribonucleic Acid Expression Correlates with Tumor Progression, Tumor Angiogenesis, Patient Survival, and Timing of Relapse in Non-Small-Cell Lung Cancer",
  106. (2004). Interleukin-8/CXCL8 is a growth factor for human lung cancer cells",
  107. (2007). Intratumoral Balance of Regulatory and Cytotoxic T Cells Is Associated With Prognosis of Hepatocellular Carcinoma After Resection",
  108. (2003). Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer",
  109. (2004). Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis",
  110. (2006). Loss of Tumor Necrosis Factor {alpha} Potentiates Transforming Growth Factor {beta}-mediated Pathogenic Tissue Response during Wound Healing",
  111. (2005). Lung Cancer: The diagnosis and treatment of lung cancer.
  112. (2007). Lung carcinomas decrease the number of monocytes/macrophages (CD14+ cells) that produce TNF-alpha",
  113. (2005). Lung defences: an overview",
  114. (2005). Macrophage and mast-cell invasion of tumor cell islets confers a marked survival advantage in non-small-cell lung cancer",
  115. (2007). Macrophage expression of IL-10 is a prognostic factor in non-small cell lung cancer",
  116. (2005). Macrophage infiltration and its prognostic implications in breast cancer: the relationship with VEGF expression and microvessel density",
  117. (2000). Macrophage infiltration in human non-small-cell lung cancer: the role of CC chemokines",
  118. (2002). Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes",
  119. (1993). Macrophages and multicellular tumor spheroids in coculture: a three-dimensional model to study tumor-host interactions. Evidence for macrophage-mediated tumor cell proliferation and migration",
  120. (2008). Malignant and non-malignant lung tissue areas are differentially populated by natural killer cells and regulatory T cells in non-small cell lung cancer",
  121. (2001). Mannose-binding lectin: targeting the microbial world for complement attack and opsonophagocytosis",
  122. (2000). Mast cell density is associated with angiogenesis and poor prognosis in pulmonary adenocarcinoma",
  123. (1989). Mast cell heterogeneity",
  124. (1996). Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF[alpha]",
  125. (2007). Mast cell tryptases and chymases in inflammation and host defense",
  126. (1997). Mast cell-tumor cell interactions: for or against tumour growth and metastasis?",
  127. (2008). Mast cells and cancer-No longer just basic science", Crit Rev.Oncol.Hematol.
  128. (2000). Mast Cells Can Amplify Airway Reactivity and Features of Chronic Inflammation in an Asthma Model in Mice",
  129. (2000). Mast cells correlate with angiogenesis and poor outcome in stage I lung adenocarcinoma",
  130. (2006). Mast Cells Enhance T Cell Activation: Importance of Mast Cell Costimulatory Molecules and Secreted TNF",
  131. (2005). Mast cells enhance T cell activation: Importance of mast cell-derived TNF",
  132. (1998). Mechanisms in the Pathogenesis of Asbestosis and Silicosis",
  133. (2004). Melanoma associated antigen (MAGE)-A3 expression in Stages I and II non-small cell lung cancer: results of a multi-center study",
  134. (2004). Meta-Analysis of Randomized Clinical Trials Comparing Cisplatin to Carboplatin in Patients With Advanced Non-Small-Cell Lung Cancer",
  135. (2001). Microenvironmental influence on macrophage regulation of angiogenesis in wounds and malignant tumors",
  136. (2008). Natural killer cell accumulation in tumors is dependent on IFN-gamma and CXCR3 ligands",
  137. (2008). Natural killer cells infiltrating human nonsmall-cell lung cancer are enriched in CD56 bright CD16(-) cells and display an impaired capability to kill tumor cells",
  138. (1999). Necrosis correlates with high vascular density and focal macrophage infiltration in invasive carcinoma of the breast",
  139. (1993). New Concepts about the Mast Cell", The New England
  140. (2002). NF-kappaB at the crossroads of life and death",
  141. (1997). Nitric oxide and macrophage function",
  142. (1991). Nitric oxide synthesis in endothelial cells: evidence for a pathway inducible by TNF-alpha",
  143. (2006). Nuclear factor-[kappa]B in cancer development and progression",
  144. (2006). p53 and HER2/neu expression in relation to chemotherapy response in patients with non-small cell lung cancer",
  145. (2006). Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer",
  146. (2006). Paradoxical roles of the immune system during cancer development",
  147. (2009). Pathogen recognition and inflammatory signaling in innate immune defenses",
  148. (2003). Pilot study of recombinant human soluble tumor necrosis factor (TNF) receptor (p75) fusion protein (TNFR:Fc; Enbrel) in patients with refractory multiple myeloma: increase in plasma TNF alpha levels during treatment",
  149. (2008). Predominant infiltration of macrophages and CD8(+) T Cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer",
  150. (2002). Prevalence of Regulatory T Cells Is Increased in Peripheral Blood and Tumor Microenvironment of Patients with Pancreas or Breast Adenocarcinoma",
  151. (2008). Prognostic Effect of Epithelial and Stromal Lymphocyte Infiltration in Non-Small Cell Lung Cancer",
  152. (2001). Prognostic significance of activated CD8(+) T cell infiltrations within esophageal carcinomas",
  153. (2003). Prognostic significance of CD8+ T cell and macrophage peritumoral infiltration in colorectal cancer",
  154. (1998). Prognostic significance of tumor necrosis factors and their receptors in nonsmall cell lung carcinoma",
  155. (2000). Prognostic value of intratumoral natural killer cells in gastric carcinoma",
  156. (2001). Progress in human tumour immunology and immunotherapy",
  157. (2006). Prostaglandin E2 activates EP2 receptors to inhibit human lung mast cell degranulation",
  158. (2004). Prostaglandin E2 Induces Degranulation-Independent Production of Vascular Endothelial Growth Factor by Human Mast Cells",
  159. (2003). Radical causes of cancer",
  160. (2004). Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy",
  161. (1997). Randomized placebo-controlled clinical trial of high-dose interleukin-2 in combination with a soluble p75 tumor necrosis factor receptor immunoglobulin G chimera in patients with advanced melanoma and renal cell carcinoma",
  162. (2002). RANTES Expression Is a Predictor of Survival in Stage I Lung Adenocarcinoma",
  163. (2000). Reactive oxygen and reactive nitrogen intermediates in innate and specific immunity",
  164. (2003). Reassessment of the microbicidal activity of reactive oxygen species and hypochlorous acid with reference to the phagocytic vacuole of the neutrophil granulocyte",
  165. (1947). Recent Advances in Cancer Research",
  166. (2000). Regular review: Tumour markers in malignancies",
  167. (2003). Regulation of angiogenesis by hypoxia: role of the HIF system",
  168. (1999). Regulation of CD 163 on human macrophages: cross-linking of CD163 induces signaling and activation",
  169. (2006). Regulatory T cells, tumour immunity and immunotherapy",
  170. (2008). Relationship between non-small cell lung cancer FDG uptake at PET, tumor histology, and Ki-67 proliferation index",
  171. (2008). Resolution of non-small-cell lung cancer after withdrawal of anti-TNF therapy",
  172. (1997). Revisions in the International System for Staging Lung Cancer",
  173. (2009). Role of alcohol in liver carcinogenesis",
  174. (2001). Role of leukocytes and endothelial cells in the development of angiogenesis in inflammation and wound healing",
  175. (1996). Role of stromal myofibroblasts infiltrating colon cancer in tumor invasion",
  176. (2002). Role of tumorassociated macrophage in malignant tumors: should the location of the infiltrated macrophages be taken into account during evaluation?",
  177. (1978). Schistosomiasis and neoplasia",
  178. (2008). Serum levels of apoptosis biomarkers, survivin and TNF-alpha in nonsmall cell lung cancer",
  179. (2000). Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies",
  180. (2006). Solid malignancies among patients in the Wegener's Granulomatosis Etanercept Trial",
  181. (2004). Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival",
  182. (2004). Strategies and mechanisms for host and pathogen survival in acute and persistent viral infections",
  183. (2008). Stromal mast cells in invasive breast cancer are a marker of favourable prognosis: a study of 4,444 cases",
  184. (2001). Synergism of Cytotoxic T Lymphocyte-associated Antigen 4 Blockade and Depletion of CD25+ Regulatory T Cells in Antitumor Therapy Reveals Alternative Pathways for Suppression of Autoreactive Cytotoxic T Lymphocyte Responses",
  185. (2002). T cell priming by dendritic cells: thresholds for proliferation, differentiation and death and intraclonal functional diversification",
  186. (2003). Targeting HIF-1 for cancer therapy",
  187. (1989). TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties",
  188. (2000). The Biology of Chemokines and their Receptors",
  189. (1992). The calciumbinding proteins MRP8 and MRP14 form a membrane-associated heterodimer in a subset of monocytes/macrophages present in acute but absent in chronic inflammatory lesions",
  190. (2004). The chemokine system in diverse forms of macrophage activation and polarization",
  191. (2003). The degree of macrophage infiltration into the cancer cell nest is a significant predictor of survival in gastric cancer patients",
  192. (2008). The development of allergic inflammation",
  193. (2001). The EUROCARE study of survival of cancer patients in Europe: aims, current status, strengths and weaknesses",
  194. (2005). the Herceptin Adjuvant (HERA) Trial Study Team
  195. (2007). The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours",
  196. (2000). The Immune System- First of Two Parts",
  197. (1997). The increasing incidence of lung adenocarcinoma: reality or artefact? A review of the epidemiology of lung adenocarcinoma",
  198. (2008). The inflammatory micro-environment in tumor progression: The role of tumorassociated macrophages",
  199. (2008). The influence of mast cell mediators on migration of SW756 cervical carcinoma cells",
  200. (2000). The influence of the microenvironment on the malignant phenotype",
  201. (2000). The inhibitory effects of transforming growth factor-beta-1 (TGF-beta1) in autoimmune diseases",
  202. (1996). The Instructive Role of Innate Immunity in the Acquired Immune Response",
  203. (2008). The International Epidemiology of Lung Cancer: geographical distribution and secular trends",
  204. (2001). The intratumoral expression of vascular endothelial growth factor and interleukin-8 associated with angiogenesis in nonsmall cell lung carcinoma patients",
  205. (2000). The Ki-67 protein: from the known and the unknown",
  206. (2007). The levels of caspase-cleaved cytokeratin 18 are elevated in serum from patients with lung cancer and helpful to predict the survival",
  207. (2005). The macrophage scavenger receptor CD163",
  208. (2001). The microenvironment of the tumour-host interface",
  209. (2000). The microscopic anatomy of experimental rat CC531 colon tumour metastases: consequences for immunotherapy?",
  210. (1998). The multifaceted roles of nitric oxide in cancer",
  211. (2005). The predictive value of CD8, CD4, CD68, and human leukocyte antigen-D-related cells in the prognosis of cutaneous malignant melanoma with vertical growth phase",
  212. (2008). The prognostic and predictive role of histology in advanced non-small cell lung cancer: a literature review",
  213. (1997). The prognostic significance of intratumoral natural killer cells in patients with colorectal carcinoma",
  214. (2005). The relationship of tryptase- and chymase-positive mast cells to angiogenesis in stage I non-small cell lung cancer",
  215. (2006). The role of the mast cell in the pathophysiology of asthma",
  216. (2002). The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies",
  217. (2008). The significance and relationship between mast cells and tumour angiogenesis in non-small cell lung carcinoma",
  218. (2007). The spectrum and clinical sequelae of human papillomavirus infection",
  219. (2003). The stromal derived factor-1/CXCL12-CXC chemokine receptor 4 biological axis in non-small cell lung cancer metastases",
  220. (2001). The TNF and TNF Receptor Superfamilies: Integrating Mammalian Biology",
  221. (1996). The tumor necrosis factor ligand and receptor families",
  222. (2007). The tumour microenvironment as a target for chemoprevention",
  223. (1998). TNF-alpha activates at least two apoptotic signaling cascades",
  224. (2006). TNF-alpha in promotion and progression of cancer",
  225. (2002). TNF-R1 Signaling: A Beautiful Pathway",
  226. (1998). TNF, apoptosis and autoimmunity: a common thread?",
  227. (2003). Toll-like receptor 2 (TLR2) and TLR4 differentially activate human mast cells",
  228. (2000). Transendothelial migration of 27E10+ human monocytes",
  229. (2001). Treatment of stage I and II non-small-cell lung cancer",
  230. (2000). Tumor associated macrophages in human prostate cancer: relation to clinicopathological variables and survival",
  231. (2006). Tumor infiltrating Foxp3+ regulatory T-cells are associated with recurrence in pathologic stage I NSCLC patients",
  232. (2002). Tumor infiltrating lymphocytes and macrophages have a potential dual role in lung cancer by supporting both host-defense and tumor progression",
  233. (2007). Tumor microenvironment: the role of the tumor stroma in cancer",
  234. (2002). Tumor necrosis factor or tumor promoting factor?",
  235. (2005). Tumor necrosis factor, cancer and anticancer therapy",
  236. (2001). Tumor structure and extracellular matrix as a possible barrier for therapeutic approaches using immune cells or adenoviruses in colorectal cancer",
  237. (1999). Tumor-associated macrophage infiltration in pulmonary adenocarcinoma: association with angiogenesis and poor prognosis",
  238. (2003). Tumour necrosis factor [alpha]: a potential target for the therapy of solid tumours",
  239. (2000). Tumour necrosis factor- [agr] and transforming growth factor- [bgr] are significantly associated with better prognosis in non-small cell lung carcinoma: putative relation with BCL-2-mediated neovascularization",
  240. (2006). Tumour necrosis factoralpha as a tumour promoter",
  241. (2006). Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy",
  242. (2004). Tumour-associated macrophages as a prototypic type II polarised phagocyte population: role in tumour progression",
  243. (2007). Tumour-derived microvesicles modulate biological activity of human monocytes",
  244. (2004). Tumour-educated macrophages promote tumour progression and metastasis",
  245. (1986). Two types of human mast cells that have distinct neutral protease compositions",
  246. (2003). Up-Regulation of Tumor Interleukin-8 Expression by Infiltrating Macrophages: Its Correlation with Tumor Angiogenesis and Patient Survival in Non-Small Cell Lung Cancer",
  247. (2003). Vaccination With Irradiated Autologous Tumor Cells Engineered to Secrete Granulocyte-Macrophage Colony-Stimulating Factor Augments Antitumor Immunity in Some Patients With Metastatic Non-Small-Cell Lung Carcinoma",
  248. (1999). Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor Induce Expression of CXCR4 on Human Endothelial Cells : In Vivo Neovascularization Induced byStromal-Derived Factor-1{alpha}",
  249. (2002). Vascular Endothelial Growth Factor Promotes Breast Carcinoma Invasion in an Autocrine Manner by Regulating the Chemokine Receptor CXCR4",
  250. (2002). Vascular Endothelial Growth Factor Secretion by Tumor-infiltrating Macrophages Essentially Supports Tumor Angiogenesis,
  251. (2006). Worldwide trends in lung cancer pathology",
  252. (2007). WWOX Expression in Different Histologic Types and Subtypes of Non-Small Cell Lung Cancer",

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