Immune alterations and emerging immunotherapeutic approaches in lung cancer

Expert Opinion on Biological Therapy

Volumn 12, Issue 7, 2012, Pages 923-937

  Dasanu, Constantin A ^a   Sethi, Nishant ^b   Ahmed, Nausheen ^b  

^a SAINT FRANCIS HOSPITAL AND MEDICAL CENTER   (United States)

^b UNIVERSITY OF CONNECTICUT HEALTH CENTER   (United States)

Author keywords

Immmunomodulator; Immune alterations; Immunotherapy; Lung cancer; Vaccine

Indexed keywords

BELAGENPUMATUCEL L; CANCER VACCINE; CARBOPLATIN; CD103 ANTIGEN; CD38 ANTIGEN; CHEMOKINE RECEPTOR CCR7; CYCLOPHOSPHAMIDE; DOCETAXEL; EMEPEPIMUT S; EPIDERMAL GROWTH FACTOR; FAS ANTIGEN; GI 4000 VACCINE; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR VACCINE; IPILIMUMAB; MELANOMA ANTIGEN 3; MUCIN 1; NIVOLUMAB; PACLITAXEL; PEMETREXED; SIPULEUCEL T; TAG VACCINE; TALACTOFERRIN; TG 4010; UNCLASSIFIED DRUG;

ANTIGEN RECOGNITION; ANTIGEN SPECIFICITY; AUTOIMMUNITY; B LYMPHOCYTE; CANCER CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CANCER SURVIVAL; CARCINOGENESIS; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CYTOKINE RELEASE; DENDRITIC CELL; DRUG EFFICACY; DRUG FEVER; DRUG SAFETY; DRUG TOLERABILITY; ENDOCRINE DISEASE; FATIGUE; FLU LIKE SYNDROME; GASTROINTESTINAL DISEASE; HUMAN; IMMUNOMODULATION; IMMUNOSUPPRESSIVE TREATMENT; LIVER DISEASE; LOCAL SKIN REACTION; LUNG CANCER; LUNG NON SMALL CELL CANCER; LYMPHOCYTOPENIA; MACROPHAGE; MELANOMA; MONOCYTE; MYALGIA; NATURAL KILLER CELL; NEUTROPHIL; OVERALL SURVIVAL; PROSTATE CANCER; REGULATORY T LYMPHOCYTE; REVIEW; SKIN TOXICITY; SURVIVAL RATE; TOXICITY; TUMOR MICROENVIRONMENT;

ADJUVANTS, IMMUNOLOGIC; ANTIBODIES, MONOCLONAL; CANCER VACCINES; CYTOKINES; HUMANS; IMMUNOTHERAPY; LUNG NEOPLASMS; LYMPHOCYTE SUBSETS; TUMOR MICROENVIRONMENT;

EID: 84862236855     PISSN: 14712598     EISSN: None     Source Type: Journal    
DOI: 10.1517/14712598.2012.685715     Document Type: Review

References (112)

1. Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin 2010;60:277-300
2. Yagui-Beltran A, Jablons DM. A translational approach to lung cancer research. Ann Thorac Cardiovasc Surg 2009;15:213-20
3. Ettinger DS, Akerley W, Bepler G, et al. Non-small cell lung cancer. J Natl Compr Canc Netw 2010;8:740-801
4. Sun S, Schiller JH, Gazdar AF. Lung cancer in never smokers-a different disease. Nat Rev Cancer 2007;7:778-90
5. Van den Heuvel MM, Burgers SA, van Zandwijk N. Immunotherapy in non-small-cell lung carcinoma: From inflammation to vaccination. Clin Lung Cancer 2009;10:99-105.. An important paper summarizing the immunotherapeutic approaches in lung cancer.
6. Sterlacci W, Wolf D, Savic S, et al. High transforming growth factor beta expression represents an important prognostic parameter for surgically resected non-small cell lung cancer. Hum Pathol 2012;43:339-49
7. Sato Y, Mukai K, Watanabe S, et al. Lymphocyte subsets in pulmonary venous and arterial blood of lung cancer patients. Jpn J Clin Oncol 1989;19:229-36
8. Wesselius LJ, Wheaton DL, Manahan-Wahl LJ, et al. Lymphocyte subsets in lung cancer. Chest 1987;91:725-9
9. Lucivero G, Pierucci G, Bonomo L. Lymphocyte subsets in peripheral blood and pleural fluid. Eur Respir J 1988;1:337-40
10. Zikos TA, Donnenberg AD, Landreneau RJ, et al. Lung T-cell subset composition at the time of surgical resection is a prognostic indicator in non-small cell lung cancer. Cancer Immunol Immunother 2011;60:819-27
11. Zhuang X, Xia X, Wang C, et al. High number of CD8+ T cells in NSCLC tissues is associated with a favorable prognosis. Appl Immunohistochem Mol Morphol 2010;18:24-8
12. Karagoz B, Bilgi O, Gumus M, et al. CD8+CD28- cells and CD4+CD25+ regulatory T cells in the peripheral blood of advanced stage lung cancer patients. Med Oncol 2010;27:29-33
13. Ye ZJ, Zhou Q, Zhang JC, et al. CD39+ regulatory T cells suppress generation and differentiation of Th17 cells in human malignant pleural effusion via a LAP-dependent mechanism. Respir Res 2011;12:77
14. Li Y, Cao ZY, Sun B, et al. Effects of IL-17A on the occurrence of lung adenocarcinoma. Cancer Biol Ther 2011;12:610-16
15. Woo EY, Yeh H, Chu CS, et al. Cutting edge: Regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation. J Immunol 2002;168:4272-6.. An important paper summarizing the abnormalities of Tregs in lung cancer.
16. Li H, Zhao H, Yu J, et al. Increased prevalence of regulatory T cells in the lung cancer microenvironment: A role of thymic stromal lymphopoietin. Cancer Immunol Immunother 2011;60:1587-96. A work delineating the alterations of Tregs in lung cancer.
17. Schneider T, Kimpfler S, Warth A, et al. Foxp3(+) regulatory T cells and natural killer cells distinctly infiltrate primary tumors and draining lymph nodes in pulmonary adenocarcinoma. J Thorac Oncol 2011;6:432-8
18. Eikawa S, Ohue Y, Kitaoka K, et al. Enrichment of Foxp3+ CD4 regulatory T cells in migrated T cells to IL-6- and IL-8-expressing tumors through predominant induction of CXCR1 by IL-6. J Immunol 2010;185:6734-40
19. Shimizu K, Nakata M, Hirami Y, et al. Tumor-infiltrating Foxp3+ regulatory T cells are correlated with cyclooxygenase-2 expression and are associated with recurrence in resected non-small cell lung cancer. J Thorac Oncol 2010;5:585-90
20. Anz D, Mueller W, Golic M, et al. CD103 is a hallmark of tumor-infiltrating regulatory T cells. Int J Cancer 2011;129:2417-26
21. Karagoz B, Bilgi O, Gumus M, et al. CD8+CD28- cells and CD4+CD25+ regulatory T cells in the peripheral blood of advanced stage lung cancer patients. Med Oncol 2010;27:29-33. A paper on T-cell alterations in lung cancer.
22. Wang RF. CD8+ regulatory T cells, their suppressive mechanisms, and regulation in cancer. Hum Immunol 2008;69:811-14
23. Wang YY, He XY, Cai YY, et al. The variation of CD4+CD25+ regulatory T cells in the periphery blood and tumor microenvironment of non-small cell lung cancer patients and the downregulation effects induced by CpG ODN. Target Oncol 2011;6:147-54
24. Gorny MK, Jezewska E, Skrzypczak A, et al. Immunoregulatory effect of T cell subsets on PWM-induced IgG synthesis by blood lymphocytes in lung cancer. Arch Immunol Ther Exp (Warsz) 1991;39:243-52
25. Takahashi T, Tagami T, Yamazaki S, et al. Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med 2000;192:303-10
26. Miotto D, Lo Cascio N, Stendardo M, et al. CD8+ T cells expressing IL-10 are associated with a favourable prognosis in lung cancer. Lung Cancer 2010;69:355-60
27. Venkataraman M, Rao DS, Iyer BS, et al. The functional deficiency of B lymphocytes in patients with lung cancer is due to inadequate T-cell help and excessive suppression by T and non-T cells. Cancer Invest 1989;7:7-16
28. van der Vliet HJ, Koon HB, Atkins MB, et al. Exploiting regulatory T-cell populations for the immunotherapy of cancer. J Immunother 2007;30:591-5
29. Sorrentino R, Morello S, Forte G, et al. B cells contribute to the antitumor activity of CpG-oligodeoxynucleotide in a mouse model of metastatic lung carcinoma. Am J Respir Crit Care Med 2011;183:1369-79
30. Yasuda M, Takenoyama M, Obata Y, et al. Tumor-infiltrating B lymphocytes as a potential source of identifying tumor antigen in human lung cancer. Cancer Res 2002;62:1751-6
31. Yuan D, Koh CY, Wilder JA. Interactions between B lymphocytes and NK cells. FASEB J 1994;8:1012-18
32. Brunda MJ, Luistro L, Warrier RR, et al. Antitumor and antimetastatic activity of interleukin 12 against murine tremors. J Exp Med 1993;178:1223-30
33. Jones HP, Wang YC, Aldridge B, et al. Lung and splenic B cells facilitate diverse effects on in vitro measures of antitumor immune responses. Cancer Immun 2008;8:4
34. Quan N, Zhang Z, Demetrikopoulos MK, et al. Evidence for involvement of B lymphocytes in the surveillance of lung metastasis in the rat. Cancer Res 1999;59:1080-9
35. Guo Y, Wu M, Chen H, et al. Effective tumor vaccine generated by fusion of hepatoma cells with activated B-lymphocytes. Science (Washington DC) 1994;263:518-20
36. Le Maux Chansac B, Moretta A, Vergnon I, et al. NK cells infiltrating a MHC class I-deficient lung adenocarcinoma display impaired cytotoxic activity toward autologous tumor cells associated with altered NK cell-triggering receptors. J Immunol 2005;175:5790-8
37. Al Omar SY, Marshall E, Middleton D, et al. Increased killer immunoglobulin-like receptor expression and functional defects in natural killer cells in lung cancer. Immunology 2011;133:94-104
38. Platonova S, Cherfils-Vicini J, Damotte D, et al. Profound coordinated alterations of intratumoral NK cell phenotype and function in lung carcinoma. Cancer Res 2011;71:5412-22
39. Kim H, Kim SH, Kim MJ, et al. EGFR inhibitors enhanced the susceptibility to NK cell-mediated lysis of lung cancer cells. J Immunother 2011;34:372-81
40. Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol 2008;8:958-69
41. Wang R, Zhang J, Chen S, et al. Tumor-associated macrophages provide a suitable microenvironment for non-small lung cancer invasion and progression. Lung Cancer 2011;74:188-96
42. Sawachi K, Shimada Y, Taniguchi H, et al. Cytotoxic effects of activated alveolar macrophages on lung carcinoma cells via cell-to-cell contact and nitric oxide. Anticancer Res 2010;30:3135-41
43. Taniguchi H, Shimada Y, Sawachi K, et al. Lipopolysaccharide-activated alveolar macrophages having cytotoxicity toward lung tumor cells through cell-to-cell binding-dependent mechanism. Anticancer Res 2010;30:3159-65
44. Coffelt SB, Chen YY, Muthana M, et al. Angiopoietin 2 stimulates TIE2-expressing monocytes to suppress T cell activation and to promote regulatory T cell expansion. J Immunol 2011;186:4183-90
45. White ES, Strom SR, Wys NL, et al. Non-small cell lung cancer cells induce monocytes to increase expression of angiogenic activity. J Immunol 2001;166:7549-55
46. Ungefroren H, Sebens S, Seidl D, et al. Interaction of tumor cells with the microenvironment. Cell Commun Signal 2011;9:18
47. Fritz JM, Dwyer-Nield LD, Malkinson AM. Stimulation of neoplastic mouse lung cell proliferation by alveolar macrophage-derived, insulin-like growth factor-1 can be blocked by inhibiting MEK and PI3K activation. Mol Cancer 2011;10:76
48. Standiford TJ, Kuick R, Bhan U, et al. TGF-beta-induced IRAK-M expression in tumor-associated macrophages regulates lung tumor growth. Oncogene 2011;30:2475-84
49. Hiraoka K, Zenmyo M, Watari K, et al. Inhibition of bone and muscle metastases of lung cancer cells by a decrease in the number of monocytes/macrophages. Cancer Sci 2008;99:1595-602
50. Ibaraki T, Muramatsu M, Takai S, et al. The relationship of tryptase- and chymase-positive mast cells to angiogenesis in stage I non-small cell lung cancer. Eur J Cardiothorac Surg 2005;28:617-21
51. Stoyanov E, Uddin M, Mankuta D, et al. Mast cells and histamine enhance the proliferation of non-small cell lung cancer cells. Lung Cancer 2012;75:38-44
52. Tataroglu C, Kargi A, Ozkal S, et al. Association of macrophages, mast cells and eosinophil leukocytes with angiogenesis and tumor stage in non-small cell lung carcinomas (NSCLC). Lung Cancer 2004;43:47-54
53. Carlini MJ, Dalurzo MC, Lastiri JM, et al. Mast cell phenotypes and microvessels in non-small cell lung cancer and its prognostic significance. Hum Pathol 2010;41:697-705
54. Dundar E, Oner U, Peker BC, et al. The significance and relationship between mast cells and tumour angiogenesis in non-small cell lung carcinoma. J Int Med Res 2008;36:88-95
55. Imada A, Shijubo N, Kojima H, et al. Mast cells correlate with angiogenesis and poor outcome in stage I lung adenocarcinoma. Eur Respir J 2000;15:1087-93
56. Ilie M, Hofman V, Ortholan C, et al. Predictive clinical outcome of the intratumoral CD66b-positive neutrophilto- CD8-positive T-cell ratio in patients with resectable nonsmall cell lung cancer. Cancer 2012;118:1726-37
57. Vikis HG, Gelman AE, Franklin A, et al. Neutrophils are required for 3- methylcholanthrene-initiated, butylated hydroxytoluene-promoted lung carcinogenesis. Mol Carcinog 2011;[Epub ahead of print]
58. Tomita M, Shimizu T, Ayabe T, et al. Preoperative neutrophil to lymphocyte ratio as a prognostic predictor after curative resection for non-small cell lung cancer. Anticancer Res 2011;31:2995-8
59. Tazzyman S, Barry ST, Ashton S, et al. Inhibition of neutrophil infiltration into A549 lung tumors in vitro and in vivo using a CXCR2-specific antagonist is associated with reduced tumor growth. Int J Cancer 2011;129:847-58
60. Carpagnano GE, Palladino GP, Lacedonia D, et al. Neutrophilic airways inflammation in lung cancer: The role of exhaled LTB-4 and IL-8. BMC Cancer 2011;11:226
61. Rotondo R, Barisione G, Mastracci L, et al. IL-8 induces exocytosis of arginase 1 by neutrophil polymorphonuclears in nonsmall cell lung cancer. Int J Cancer 2009;125:887-93
62. Halder SK, Cho YJ, Datta A, et al. Elucidating the mechanism of regulation of transforming growth factor beta Type II receptor expression in human lung cancer cell lines. Neoplasia 2011;13:912-22. An important work elucidating the mechanism of regulation of TGF b in lung cancer.
63. Gonzalez-Santiago AE, Mendoza-Topete LA, Sanchez-Llamas F, et al. TGF-beta1 serum concentration as a complementary diagnostic biomarker of lung cancer: Establishment of a cut-point value. J Clin Lab Anal 2011;25:238-43
64. Xu CC, Wu LM, Sun W, et al. Effects of TGF-beta signaling blockade on human A549 lung adenocarcinoma cell lines. Mol Med Rep 2011;4:1007-15
65. Zhang HJ, Wang HY, Zhang HT, et al. Transforming growth factor-beta1 promotes lung adenocarcinoma invasion and metastasis by epithelial-to- mesenchymal transition. Mol Cell Biochem 2011;355:309-14
66. Chow G, Tauler J, Mulshine JL. Cytokines and growth factors stimulate hyaluronan production: Role of hyaluronan in epithelial to mesenchymal-like transition in non-small cell lung cancer. J Biomed Biotechnol 2010;2010:485468
67. Felaco P, Castellani ML, De Lutiis MA, et al. IL-32: A newly-discovered proinflammatory cytokine. Biol Regul Homeost Agents 2009;23:141-7
68. Sculier JP, Berghmans T, Meert AP. Update in lung cancer and mesothelioma 2009. Am J Respir Crit Care Med 2010;181:773-81
69. Sorrentino C, Di Carlo E. Expression of IL-32 in human lung cancer is related to the histotype and metastatic phenotype. Am J Respir Crit Care Med 2009;180:769-79
70. Chen X, Xie Q, Cheng X, et al. Role of interleukin-17 in lymphangiogenesis in non-small-cell lung cancer: Enhanced production of vascular endothelial growth factor C in non-small-cell lung carcinoma cells. Cancer Sci 2010;101:2384-90
71. Chen X, Wan J, Liu J, et al. Increased IL-17-producing cells correlate with poor survival and lymphangiogenesis in NSCLC patients. Lung Cancer 2010;69:348-54
72. Ankathatti Munegowda M, Deng Y, Mulligan SJ, et al. Th17 and Th17-stimulated CD8+ T cells play a distinct role in Th17-induced preventive and therapeutic antitumor immunity. Cancer Immunol Immunother 2011;60:1473-84
73. Carmi Y, Rinott G, Dotan S, et al. Microenvironment-derived IL-1 and IL-17 interact in the control of lung metastasis. J Immunol 2011;186:3462-71
74. Wang zJ, Ding Q, Shi Y, et al. The interleukin-10-1082 promoter polymorphism and cancer risk: A meta-analysis. Mutagenesis 2012;27:305-12
75. Miotto D, Lo Cascio N, Stendardo M, et al. CD8+ T cells expressing IL-10 are associated with a favourable prognosis in lung cancer. Lung Cancer 2010;69:355-60
76. Zeng L, O'Connor C, Zhang J, et al. IL-10 promotes resistance to apoptosis and metastatic potential in lung tumor cell lines. Cytokine 2010;49:294-302
77. Ho MY, Leu SJ, Sun GH, et al. IL-27 directly restrains lung tumorigenicity by suppressing cyclooxygenase-2-mediated activities. J Immunol 2009;183:6217-26
78. Tyagi A, Agarwal C, Dwyer-Nield LD, et al. Silibinin modulates TNF-alpha and IFN-gamma mediated signaling to regulate COX2 and iNOS expression in tumorigenic mouse lung epithelial LM2 cells. Mol Carcinog 2011;[Epub ahead of print]
79. Park SY, Lee HS, Jang HJ, et al. Tumor necrosis as a prognostic factor for stage IA non-small cell lung cancer. Ann Thorac Surg 2011;91:1668-73
80. Wang J, Cao C, Luo H, et al. Tumour necrosis factor alpha -308G/A polymorphism and risk of the four most frequent cancers: A meta-analysis. Int J Immunogenet 2011;38:311-20
81. Shen CH, Talay O, Mahajan VS, et al. Antigen-bearing dendritic cells regulate the diverse pattern of memory CD8 T-cell development in different tissues. Proc Natl Acad Sci USA 2010;107:22587-92
82. Bergeron A, El-Hage F, Kambouchner M, et al. Characterisation of dendritic cell subsets in lung cancer micro-environments. Eur Respir J 2006;28:1170-7
83. Schneider T, Hoffmann H, Dienemann H, et al. Non-small cell lung cancer induces an immunosuppressive phenotype of dendritic cells in tumor microenvironment by upregulating B7-H3. J Thorac Oncol 2011;6:1162-8. An paper summarizing the abnormalities of dendritic cells in lung cancer.
84. Hsu YL, Huang MS, Cheng DE, et al. Lung tumor-associated dendritic cell-derived amphiregulin increased cancer progression. J Immunol 2011;187:1733-44
85. Condon TV, Sawyer RT, Fenton MJ, et al. Lung dendritic cells at the innate-adaptive immune interface. J Leukoc Biol 2011;90:883-95
86. Mu CY, Huang JA, Chen Y, et al. High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation. Med Oncol 2011;28:682-8
87. Kato M, Nakamura Y, Suda T, et al. Enhanced anti-tumor immunity by superantigen-pulsed dendritic cells. Cancer Immunol Immunother 2011;60:1029-38
88. Zhong R, Teng J, Han B, et al. Dendritic cells combining with cytokine-induced killer cells synergize chemotherapy in patients with late-stage non-small cell lung cancer. Cancer Immunol Immunother 2011;60:1497-502
89. Chen J, Cao X, Xiu Q. Treatment of spontaneous metastatic lung cancer with tumor antigen-pulsed, interleukin-18 gene-modified dendritic cells. Zhonghua Yi Xue Za Zhi 2001;81:779-82
90. Yadav A, Kumar B, Datta J, et al. IL-6 Promotes head and neck tumor metastasis by inducing epithelial-mesenchymal transition via the JAK-STAT3-SNAIL signaling pathway. Mol Cancer Res 2011;9:1658-67
91. Heinrich EL, Walser TC, Krysan K, et al. The inflammatory tumor microenvironment, epithelial mesenchymal transition and lung carcinogenesis. Cancer Microenviron 2011;[Epub ahead of print]
92. Gastman BR, Atarashi Y, Reichert TE, et al. Fas ligand is expressed on human squamous cell carcinomas of the head and neck, and it promotes apoptosis of T lymphocytes. Cancer Res 1999;59:5356-64
93. Whiteside TL. Immune responses to malignancies. J Allergy Clin Immunol 2010;125:S272-83
94. Johansson M, Denardo DG, Coussens LM. Polarized immune responses differentially regulate cancer development. Immunol Rev 2008;222:145-54
95. Marincola FM, Jaffee EM, Hicklin DJ, et al. Escape of human solid tumors from T-cell recognition: Molecular mechanisms and functional significance. Adv Immunol 2000;74:181-273
96. West HJ. Novel targeted agents for lung cancer. Clin Lung Cancer 2009;10:S41-6
97. Qiao G, Li Z, Molinero L, et al. T-cell receptor-induced NF-kappaB activation is negatively regulated by E3 ubiquitin ligase Cbl-b. Mol Cell Biol 2008;28:2470-80
98. Otsuka S, Bebb G. The CXCR4/SDF-1 chemokine receptor axis: A new target therapeutic for non-small cell lung cancer. J Thorac Oncol 2008;3:1379-83
99. Burger JA, Stewart DJ, Wald O, et al. Potential of CXCR4 antagonists for the treatment of metastatic lung cancer. Expert Rev Anticancer Ther 2011;11:621-30
100. Probst HC, McCoy K, Okazaki T, et al. Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4. Nat Immunol 2005;6:280-6 .. An important work delineating the role of PD-1 and CTLA-4 molecule and the rationale for their blockade.
101. Takahashi Y, Ishii G, Taira T, et al. Fibrous stroma is associated with poorer prognosis in lung squamous cell carcinoma patients. J Thorac Oncol 2011;6:1460-7
102. Kawase A, Ishii G, Nagai K, et al. Podoplanin expression by cancer associated fibroblasts predicts poor prognosis of lung adenocarcinoma. Int J Cancer 2008;123:1053-9
103. Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711-23
104. Lynch TJ, Bondarenko IN, Luft A, et al. Phase II trial of ipilimumab (IPI) and paclitaxel/carboplatin (P/C) in first-line stage IIIb/IV non-small cell lung cancer (NSCLC). 2010 ASCO Ann Meeting Proc 28. J Clin Oncol 2010;15:7531. An paper summarizing the effectiveness of ipilimumab therapy in lung cancer.
105. Brahmer JR, Drake CG, Wollner I, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: Safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol 2010;28:3167-75
106. Flies DB, Sandler BJ, Sznol M, et al. Blockade of the B7-H1/PD-1 pathway for cancer immunotherapy. Yale J Biol Med 2011;84:409-21. An paper summarizing the results of PD-1blockade in immunotherapy of lung cancer.
107. Parikh PM, Vaid A, Advani SH, et al. Randomized, double-blind, placebo-controlled phase II study of single-agent oral talactoferrin in patients with locally advanced or metastatic non-small-cell lung cancer that progressed after chemotherapy. J Clin Oncol 2011;29:4129-36
108. Digumarti R, Wang Y, Raman G, et al. A randomized, double-blind, placebo-controlled, phase II study of oral talactoferrin in combination with carboplatin and paclitaxel in previously untreated locally advanced or metastatic non-small cell lung cancer. J Thorac Oncol 2011;6:1098-103
109. Mellstedt H, Vansteenkiste J, Thatcher N. Vaccines for the treatment of non-small cell lung cancer: Investigational approaches and clinical experience. Lung Cancer 2011;73:11-17.. An important review summarizing the immunotherapeutic approaches in lung cancer.
110. Roberts PJ, Stinchcombe TE, Der CJ, et al. Personalized medicine in non-small-cell lung cancer: Is KRAS a useful marker in selecting patients for epidermal growth factor receptor-targeted therapy?J Clin Oncol 2010;28:4769-77
111. Kaur A, Dasanu CA. Rapidly progressive colonic dysplasia/neoplasia in a series of treated lung cancer patients: Is paclitaxel involved?J Oncol Pharm Pract 2012; [Epub ahead of print]
112. Neuville M, Borie R, Rodier JM, et al. Pneumocystis pneumonia in a patient treated with pemetrexed for non small cell lung cancer. Rev Mal Respir 2011;28:97-100