Dunn, G. P., Old, L. J. & Schreiber, R. D.
The three Es of cancer immunoediting. Annu. Rev. Immunol.
22, 329–360 (2004).
Koebel, C. M.
et al. Adaptive immunity maintains occult cancer in an equilibrium state. Nature
450, 903–907 (2007).
Schreiber, R. D., Old, L. J. & Smyth, M. J.
Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science
331, 1565–1570 (2011).
et al. IFNγ and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature
410, 1107–1111 (2001).
et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science
313, 1960–1964 (2006).
et al. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J. Clin. Oncol.
29, 610–618 (2011).
Hanahan, D. & Weinberg, R. A.
Hallmarks of cancer: the next generation. Cell
144, 646–674 (2011).
Galon, J., Fridman, W. H. & Pages, F.
The adaptive immunologic microenvironment in colorectal cancer: a novel perspective. Cancer Res.
67, 1883–1886 (2007).
et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res.
13, 2498–2504 (2003).
et al. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics
25, 1091–1093 (2009).
et al. Biomolecular network reconstruction identifies T-cell homing factors associated with survival in colorectal cancer. Gastroenterology
138, 1429–1440 (2010).
Mantovani, A., Allavena, P., Sica, A. & Balkwill, F.
Cancer-related inflammation. Nature
454, 436–444 (2008).
Dieu-Nosjean, M. C.
et al. Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures. J. Clin. Oncol.
26, 4410–4417 (2008).
et al. Localization and density of immune cells in the invasive margin of human colorectal cancer liver metastases are prognostic for response to chemotherapy. Cancer Res.
71, 5670–5677 (2011).
et al. Proliferative activity of intratumoral CD8+ T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity. Cancer Res.
61, 5132–5136 (2001).
Curiel, T. J.
et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nature Med.
10, 942–949 (2004).
Bates, G. J.
et al. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J. Clin. Oncol.
24, 5373–5380 (2006).
et al. Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome. Cancer Res.
69, 2000–2009 (2009).
et al. Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients. Gastroenterology
132, 2328–2339 (2007).
et al. Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection. J. Clin. Oncol.
25, 2586–2593 (2007).
Grabenbauer, G. G., Lahmer, G., Distel, L. & Niedobitek, G.
Tumor-infiltrating cytotoxic T cells but not regulatory T cells predict outcome in anal squamous cell carcinoma. Clin. Cancer Res.
12, 3355–3360 (2006).
Heimberger, A. B.
et al. Incidence and prognostic impact of FoxP3+ regulatory T cells in human gliomas. Clin. Cancer Res.
14, 5166–5172 (2008).
et al. Leukocyte infiltration and tumor cell plasticity are parameters of aggressiveness in primary cutaneous melanoma. Cancer Immunol. Immunother.
57, 97–106 (2008).
Jacobs, J. F.
et al. Prognostic significance and mechanism of Treg infiltration in human brain tumors. J. Neuroimmunol
225, 195–199 (2010).
et al. FOXP3+ cell density in primary tumor has no prognostic impact in patients with cutaneous malignant melanoma. Pathol. Oncol. Res.
16, 303–309 (2010).
Mahmoud, S. M.
et al. An evaluation of the clinical significance of FOXP3+ infiltrating cells in human breast cancer. Breast Cancer Res. Treat.
127, 99–108 (2011).
et al. Localisation pattern of Foxp3+ regulatory T cells is associated with clinical behaviour in gastric cancer. Br. J. Cancer
98, 148–153 (2008).
Sinicrope, F. A.
et al. Intraepithelial effector (CD3+)/regulatory (FoxP3+) T-cell ratio predicts a clinical outcome of human colon carcinoma. Gastroenterology
137, 1270–1279 (2009).
Zhang, Y. L.
et al. Different subsets of tumor infiltrating lymphocytes correlate with NPC progression in different ways. Mol. Cancer
9, 4 (2010).
et al. Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers. Clin. Cancer Res.
12, 465–472 (2006).
et al. High numbers of tumor-infiltrating FOXP3-positive regulatory T cells are associated with improved overall survival in follicular lymphoma. Blood
108, 2957–2964 (2006).
Frey, D. M.
et al. High frequency of tumor-infiltrating FOXP3+ regulatory T cells predicts improved survival in mismatch repair-proficient colorectal cancer patients. Int. J. Cancer
126, 2635–2643 (2010).
et al. Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer. Cancer Immunol. Immunother.
58, 449–459 (2009).
et al. High density of FOXP3-positive T cells infiltrating colorectal cancers with microsatellite instability. Br. J. Cancer
99, 1867–1873 (2008).
et al. Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer. J. Clin. Oncol.
27, 186–192 (2009).
et al. Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer. Cancer Res.
71, 1263–1271 (2011).
et al. Correlation of high numbers of intratumoral FOXP3+ regulatory T cells with improved survival in germinal center-like diffuse large B-cell lymphoma, follicular lymphoma and classical Hodgkin's lymphoma. Haematologica
93, 193–200 (2008).
Winerdal, M. E.
et al. FOXP3 and survival in urinary bladder cancer. BJU Int.
108, 1672–1678 (2011).
et al. Interleukin-17 inhibits tumor cell growth by means of a T-cell-dependent mechanism. Blood
99, 2114–2121 (2002).
et al. Interleukin 17, a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumors in nude mice. Cancer Res.
59, 3698–3704 (1999).
Wilke, C. M.
et al. Th17 cells in cancer: help or hindrance?
32, 643–649 (2011).
Yoon, N. K.
et al. Higher levels of GATA3 predict better survival in women with breast cancer. Hum. Pathol.
41, 1794–1801 (2010).
et al. Prognostic impact of tumour-infiltrating Th2 and regulatory T cells in classical Hodgkin lymphoma. Hematol. Oncol.
27, 31–39 (2009).
et al. The prognostic significance of intratumoral natural killer cells in patients with colorectal carcinoma. Cancer
79, 2320–2328 (1997).
et al. Prognostic value of intratumoral natural killer cells in gastric carcinoma. Cancer
88, 577–583 (2000).
Villegas, F. R.
et al. Prognostic significance of tumor infiltrating natural killer cells subset CD57 in patients with squamous cell lung cancer. Lung Cancer
35, 23–28 (2002).
Donskov, F. & von der Maase, H.
Impact of immune parameters on long-term survival in metastatic renal cell carcinoma. J. Clin. Oncol.
24, 1997–2005 (2006).
Zhu, L. Y., Zhou, J., Liu, Y. Z. & Pan, W. D.
Prognostic significance of natural killer cell infiltration in hepatocellular carcinoma. Ai Zheng
28, 1198–1202 (2009).
et al. Profound coordinated alterations of intratumoral NK cell phenotype and function in lung carcinoma. Cancer Res.
71, 5412–5422 (2011).
et al. Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity. J. Clin. Invest.
121, 3609–3622 (2011).
et al. Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions. BMC Cancer
9, 186 (2009).
et al. Primary human tumor cells expressing CD155 impair tumor targeting by down-regulating DNAM-1 on NK cells. J. Immunol.
183, 4921–4930 (2009).
et al. Differing phenotypes between intraepithelial and stromal lymphocytes in early-stage tongue cancer. Cancer Res.
67, 11195–11201 (2007).
Schleypen, J. S.
et al. Renal cell carcinoma-infiltrating natural killer cells express differential repertoires of activating and inhibitory receptors and are inhibited by specific HLA class I allotypes. Int. J. Cancer
106, 905–912 (2003).
Wong, S. C.
et al. Macrophage polarization to a unique phenotype driven by B cells. Eur. J. Immunol.
40, 2296–2307 (2010).
et al. FcRγ activation regulates inflammation-associated squamous carcinogenesis. Cancer Cell
17, 121–134 (2010).
B cells and macrophages in cancer: yin and yang. Nature Med.
17, 285–286 (2011).
Olkhanud, P. B.
et al. Tumor-evoked regulatory B cells promote breast cancer metastasis by converting resting CD4 T cells to T-regulatory cells. Cancer Res.
71, 3505–3515 (2011).
Coronella-Wood, J. A. & Hersh, E. M.
Naturally occurring B-cell responses to breast cancer. Cancer Immunol. Immunother.
52, 715–738 (2003).
Coronella, J. A.
et al. Evidence for an antigen-driven humoral immune response in medullary ductal breast cancer. Cancer Res.
61, 7889–7899 (2001).
et al. Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors. PLoS ONE
4, e6412 (2009).
DiLillo, D. J., Yanaba, K. & Tedder, T. F.
B cells are required for optimal CD4+ and CD8+ T cell tumor immunity: therapeutic B cell depletion enhances B16 melanoma growth in mice. J. Immunol.
184, 4006–4016 (2010).
et al. In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer. J. Clin. Oncol.
27, 5944–5951 (2009).
et al. Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes. Clin. Cancer Res.
14, 5158–5165 (2008).
et al. Gene pathways associated with prognosis and chemotherapy sensitivity in molecular subtypes of breast cancer. J. Natl Cancer Inst.
103, 264–272 (2011).
Sotiriou, C. & Pusztai, L.
Gene-expression signatures in breast cancer. N. Engl. J. Med.
360, 790–800 (2009).
Andre, F., Berrada, N. & Desmedt, C.
Implication of tumor microenvironment in the resistance to chemotherapy in breast cancer patients. Curr. Opin. Oncol.
22, 547–551 (2010).
et al. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J. Clin. Oncol.
28, 105–113 (2010).
Gajewski, T. F., Louahed, J. & Brichard, V. G.
Gene signature in melanoma associated with clinical activity: a potential clue to unlock cancer immunotherapy. Cancer J.
16, 399–403 (2010).
Altenburg, A., Baldus, S. E., Smola, H., Pfister, H. & Hess, S.
CD40 ligand-CD40 interaction induces chemokines in cervical carcinoma cells in synergism with IFN-γ. J. Immunol.
162, 4140–4147 (1999).
et al. Favorable prognosis of renal cell carcinoma with increased expression of chemokines associated with a Th1-type immune response. Cancer Sci.
97, 780–786 (2006).
et al. Increased mRNA expression of chemokines in hepatocellular carcinoma with tumor-infiltrating lymphocytes. J. Gastroenterol. Hepatol
22, 690–696 (2007).
et al. Chemokine-driven lymphocyte infiltration: an early intratumoural event determining long-term survival in resectable hepatocellular carcinoma. Gut
61, 427–438 (2011).
et al. Strong expression of the lymphoattractant C-X-C chemokine Mig is associated with heavy infiltration of T cells in human malignant melanoma. J. Pathol.
189, 552–558 (1999).
et al. Human solid tumors contain high endothelial venules: association with T- and B-lymphocyte infiltration and favorable prognosis in breast cancer. Cancer Res.
71, 5678–5687 (2011).
de Chaisemartin, L.
et al. Characterization of chemokines and adhesion molecules associated with T cell presence in tertiary lymphoid structures in human lung cancer. Cancer Res.
71, 6391–6399 (2011).
Mlecnik, B., Bindea, G., Pages, F. & Galon, J.
Tumor immunosurveillance in human cancers. Cancer Metastasis Rev.
30, 5–12 (2011).
et al. Tumor microenvironment is multifaceted. Cancer Metastasis Rev.
30, 13–25 (2011).
et al. Coordination of intratumoral immune reaction and human colorectal cancer recurrence. Cancer Res.
69, 2685–2693 (2009).
Gabrilovich, D. I., Ishida, T., Nadaf, S., Ohm, J. E. & Carbone, D. P.
Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function. Clin. Cancer Res.
5, 2963–2970 (1999).
et al. A decrease of regulatory T cells correlates with overall survival after sunitinib-based antiangiogenic therapy in metastatic renal cancer patients. J. Immunother.
33, 991–998 (2010).
Hood, L., Heath, J. R., Phelps, M. E. & Lin, B.
Systems biology and new technologies enable predictive and preventative medicine. Science
306, 640–643 (2004).
Broussard, E. K. & Disis, M. L.
TNM staging in colorectal cancer: T is for T cell and M is for memory. J. Clin. Oncol.
29, 601–603 (2011).
Ogino, S., Galon, J., Fuchs, C. S. & Dranoff, G.
Cancer immunology-analysis of host and tumor factors for personalized medicine. Nature Rev. Clin. Oncol.
8, 711–719 (2011).
Hodi, F. S.
et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med.
363, 711–723 (2010).
Kline, J. & Gajewski, T. F.
Clinical development of mAbs to block the PD1 pathway as an immunotherapy for cancer. Curr. Opin. Investig Drugs
11, 1354–1359 (2011).
et al. PD-1 blockade by CT-011, anti-PD-1 antibody, enhances ex vivo T-cell responses to autologous dendritic cell/myeloma fusion vaccine. J. Immunother.
34, 409–418 (2010).
Waldmann, T. A.
Effective cancer therapy through immunomodulation. Annu. Rev. Med.
57, 65–81 (2006).
et al. Dacarbazine promotes stromal remodeling and lymphocyte infiltration in cutaneous melanoma lesions. J. Invest. Dermatol.
131, 1896–1905 (2011).
Zitvogel, L., Apetoh, L., Ghiringhelli, F. & Kroemer, G.
Immunological aspects of cancer chemotherapy. Nature Rev. Immunol.
8, 59–73 (2008).
Ko, J. S.
et al. Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin. Cancer Res.
15, 2148–2157 (2009).
Yang, J. C.
et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N. Engl. J. Med.
349, 427–434 (2003).
Teng, M. W.
et al. Conditional regulatory T-cell depletion releases adaptive immunity preventing carcinogenesis and suppressing established tumor growth. Cancer Res.
70, 7800–7809 (2010).
et al. Anti-ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti-PD-1 or anti-CD137 mAb therapy. Proc. Natl Acad. Sci. USA
108, 7142–7147 (2011).
Finn, O. J.
Cancer immunology. N. Engl. J. Med.
358, 2704–2715 (2008).
Phan, G. Q.
et al. Immunization of patients with metastatic melanoma using both class I- and class II-restricted peptides from melanoma-associated antigens. J. Immunother.
26, 349–356 (2003).
Rosenberg, S. A.
et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin. Cancer Res.
17, 4550–4557 (2011).
Beer, T. M.
et al. Randomized trial of autologous cellular immunotherapy with sipuleucel-T in androgen-dependent prostate cancer. Clin. Cancer Res.
17, 4558–4567 (2011).
Kantoff, P. W.
et al. Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J. Clin. Oncol.
28, 1099–1105 (2010).
Abes, R., Gelize, E., Fridman, W. H. & Teillaud, J. L.
Long-lasting antitumor protection by anti-CD20 antibody through cellular immune response. Blood
116, 926–934 (2010).
et al. Trial Watch, monoclonal antibodies in cancer therapy. Oncoimmunology
1, 28–37 (2012).
et al. The therapeutic effect of anti-HER2/neu antibody depends on both innate and adaptive immunity. Cancer Cell
18, 160–170 (2010).
Clark, W. H. Jr.
et al. Model predicting survival in stage I melanoma based on tumor progression. J. Natl Cancer Inst.
81, 1893–1904 (1989).
Clemente, C. G.
et al. Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer
77, 1303–1310 (1996).
et al. Evidence for in situ amplification of cytotoxic T-lymphocytes with antitumor activity in a human regressive melanoma. Cancer Res.
53, 3569–3573 (1993).
Tefany, F. J., Barnetson, R. S., Halliday, G. M., McCarthy, S. W. & McCarthy, W. H.
Immunocytochemical analysis of the cellular infiltrate in primary regressing and non-regressing malignant melanoma. J. Invest. Dermatol.
97, 197–202 (1991).
et al. Utility of tumour-infiltrating CD25+FOXP3+ regulatory T cell evaluation in predicting local recurrence in vertical growth phase cutaneous melanoma. Oncol. Rep.
18, 1115–1122 (2007).
et al. Intratumoral forkhead box P3-positive regulatory T cells predict poor survival in cyclooxygenase-2-positive uveal melanoma. Cancer
116, 2224–2233 (2010).
Reichert, T. E., Scheuer, C., Day, R., Wagner, W. & Whiteside, T. L.
The number of intratumoral dendritic cells and zeta-chain expression in T cells as prognostic and survival biomarkers in patients with oral carcinoma. Cancer
91, 2136–2147 (2001).
Shibuya, T. Y.
et al. Clinical significance of poor CD3 response in head and neck cancer. Clin. Cancer Res.
8, 745–751 (2002).
et al. High expression of lymphocyte-associated genes in node-negative HER2+ breast cancers correlates with lower recurrence rates. Cancer Res.
67, 10669–10676 (2007).
Mahmoud, S. M.
et al. Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J. Clin. Oncol.
29, 1949–1955 (2011).
Marrogi, A. J.
et al. Study of tumor infiltrating lymphocytes and transforming growth factor-β as prognostic factors in breast carcinoma. Int. J. Cancer
74, 492–501 (1997).
Menegaz, R. A., Michelin, M. A., Etchebehere, R. M., Fernandes, P. C. & Murta, E. F.
Peri- and intratumoral T and B lymphocytic infiltration in breast cancer. Eur. J. Gynaecol. Oncol.
29, 321–326 (2008).
Oldford, S. A.
et al. Tumor cell expression of HLA-DM associates with a Th1 profile and predicts improved survival in breast carcinoma patients. Int. Immunol.
18, 1591–1602 (2006).
Teschendorff, A. E.
et al. Improved prognostic classification of breast cancer defined by antagonistic activation patterns of immune response pathway modules. BMC Cancer
10, 604 (2010).
Camp, B. J., Dyhrman, S. T., Memoli, V. A., Mott, L. A. & Barth, R. J. Jr.
In situ cytokine production by breast cancer tumor-infiltrating lymphocytes. Ann. Surg. Oncol.
3, 176–184 (1996).
et al. Clinical significance of immune cell infiltration within gallbladder cancer. Br. J. Cancer
89, 1736–1742 (2003).
et al. CD8 tumor-infiltrating lymphocytes are predictive of survival in muscle-invasive urothelial carcinoma. Proc. Natl Acad. Sci. USA
104, 3967–3972 (2007).
et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N. Engl. J. Med.
348, 203–213 (2003).
et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc. Natl Acad. Sci. USA
102, 18538–18543 (2005).
et al. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc. Natl Acad. Sci. USA
104, 3360–3365 (2007).
et al. Relative expression levels of Th1 and Th2 cytokine mRNA are independent prognostic factors in patients with ovarian cancer. Oncol. Rep.
13, 1153–1158 (2005).
et al. Interferon-γ expression is an independent prognostic factor in ovarian cancer. Am. J. Obstet. Gynecol.
191, 1598–1605 (2004).
et al. Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood
114, 1141–1149 (2009).
et al. CD4+ and CD8+ T cells cooperate to improve prognosis of patients with esophageal squamous cell carcinoma. Cancer Res.
63, 1555–1559 (2003).
Schumacher, K., Haensch, W., Roefzaad, C. & Schlag, P. M.
Prognostic significance of activated CD8+ T cell infiltrations within esophageal carcinomas. Cancer Res.
61, 3932–3936 (2001).
van Sandick, J. W.
et al. Lymphocyte subsets and T h1/T h2 immune responses in patients with adenocarcinoma of the oesophagus or oesophagogastric junction: relation to pTNM stage and clinical outcome. Cancer Immunol. Immunother.
52, 617–624 (2003).
et al. The accumulation and prognosis value of tumor infiltrating IL-17 producing cells in esophageal squamous cell carcinoma. PLoS ONE
6, e18219 (2011).
Baier, P. K.
et al. Analysis of the T cell receptor variability of tumor-infiltrating lymphocytes in colorectal carcinomas. Tumour Biol.
19, 205–212 (1998).
et al. Differential significance of tumour infiltrating lymphocytes in sporadic mismatch repair deficient versus proficient colorectal cancers: a potential role for dysregulation of the transforming growth factor-β pathway. Eur. J. Cancer
43, 624–631 (2007).
Dalerba, P., Maccalli, C., Casati, C., Castelli, C. & Parmiani, G.
Immunology and immunotherapy of colorectal cancer. Crit. Rev. Oncol. Hematol.
46, 33–57 (2003).
Diederichsen, A. C., Hjelmborg, J. B., Christensen, P. B., Zeuthen, J. & Fenger, C.
Prognostic value of the CD4+/CD8+ ratio of tumour infiltrating lymphocytes in colorectal cancer and HLA-DR expression on tumour cells. Cancer Immunol. Immunother.
52, 423–428 (2003).
Graham, D. M. & Appelman, H. D.
Crohn's-like lymphoid reaction and colorectal carcinoma: a potential histologic prognosticator. Mod. Pathol.
3, 332–335 (1990).
et al. The localization and density of immune cells in primary tumors of human metastatic colorectal cancer shows an association with response to chemotherapy. Cancer Immun.
9, 1 (2009).
Harrison, J. C., Dean, P. J., el-Zeky, F. & Vander Zwaag, R.
From Dukes through Jass: pathological prognostic indicators in rectal cancer. Hum. Pathol.
25, 498–505 (1994).
Jass, J. R.
Lymphocytic infiltration and survival in rectal cancer. J. Clin. Pathol.
39, 585–589 (1986).
Lee, W. S., Park, S., Lee, W. Y., Yun, S. H. & Chun, H. K.
Clinical impact of tumor-infiltrating lymphocytes for survival in stage II colon cancer. Cancer
116, 5188–5199 (2010).
et al. CD8+ lymphocytes/ tumour-budding index: an independent prognostic factor representing a 'pro-/anti-tumour' approach to tumour host interaction in colorectal cancer. Br. J. Cancer
101, 1382–1392 (2009).
Menon, A. G.
et al. Immune system and prognosis in colorectal cancer: a detailed immunohistochemical analysis. Lab. Invest.
84, 493–501 (2004).
et al. CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res.
58, 3491–3494 (1998).
et al. Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer, and prognosis: cohort study and literature review. J. Pathol.
222, 350–366 (2010).
et al. Effector memory T cells, early metastasis, and survival in colorectal cancer. N. Engl. J. Med.
353, 2654–2666 (2005).
et al. Prognostic role of CD8+ tumor-infiltrating lymphocytes in stage III colorectal cancer with and without microsatellite instability. Hum. Pathol.
35, 808–816 (2004).
Ropponen, K. M., Eskelinen, M. J., Lipponen, P. K., Alhava, E. & Kosma, V. M.
Prognostic value of tumour-infiltrating lymphocytes (TILs) in colorectal cancer. J. Pathol.
182, 318–324 (1997).
Dahlin, A. M.
et al. Colorectal cancer prognosis depends on T-cell infiltration and molecular characteristics of the tumor. Mod. Pathol.
24, 671–682 (2011).
Nagtegaal, I. D.
et al. Local and distant recurrences in rectal cancer patients are predicted by the nonspecific immune response; specific immune response has only a systemic effect-a histopathological and immunohistochemical study. BMC Cancer
1, 7 (2001).
et al. Lymphocytic reaction to colorectal cancer is associated with longer survival, independent of lymph node count, microsatellite instability, and CpG island methylator phenotype. Clin. Cancer Res.
15, 6412–6420 (2009).
et al. IL-17 is associated with poor prognosis and promotes angiogenesis via stimulating VEGF production of cancer cells in colorectal carcinoma. Biochem. Biophys. Res. Commun.
407, 348–354 (2011).
Jensen, H. K., Donskov, F., Nordsmark, M., Marcussen, N. & von der Maase, H.
Increased intratumoral FOXP3-positive regulatory immune cells during interleukin-2 treatment in metastatic renal cell carcinoma. Clin. Cancer Res.
15, 1052–1058 (2009).
et al. Tumour-infiltrating lymphocytes: a prognostic factor of PSA-free survival in patients with local prostate carcinoma treated by radical prostatectomy. Anticancer Res.
25, 4435–4438 (2005).
Richardsen, E., Uglehus, R. D., Due, J., Busch, C. & Busund, L. T.
The prognostic impact of M-CSF, CSF-1 receptor, CD68 and CD3 in prostatic carcinoma. Histopathology
53, 30–38 (2008).
Vesalainen, S., Lipponen, P., Talja, M. & Syrjanen, K.
Histological grade, perineural infiltration, tumour-infiltrating lymphocytes and apoptosis as determinants of long-term prognosis in prostatic adenocarcinoma. Eur. J. Cancer
30A, 1797–1803 (1994).
Al-Shibli, K. I.
et al. Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer. Clin. Cancer Res.
14, 5220–5227 (2008).
Hiraoka, N., Onozato, K., Kosuge, T. & Hirohashi, S.
Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin. Cancer Res.
12, 5423–5434 (2006).
et al. Prognostic significance of T helper 1 and 2 and T cytotoxic 1 and 2 cells in patients with non-small cell lung cancer. Anticancer Res.
25, 2027–2031 (2005).
et al. Predominant infiltration of macrophages and CD8+ T Cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer. Cancer
113, 1387–1395 (2008).
et al. CD4+ T cells in cancer stroma, not CD8+ T cells in cancer cell nests, are associated with favorable prognosis in human non-small cell lung cancers. Cancer Sci.
94, 1003–1009 (2003).
et al. Increased IL-17-producing cells correlate with poor survival and lymphangiogenesis in NSCLC patients. Lung Cancer
69, 348–354 (2010).
Petersen, R. P.
et al. Tumor infiltrating Foxp3+ regulatory T-cells are associated with recurrence in pathologic stage I NSCLC patients. Cancer
107, 2866–2872 (2006).
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.
5, 585–590 (2010).
et al. Prognostic potential of FOXP3 expression in non-small cell lung cancer cells combined with tumor-infiltrating regulatory T cells. Lung Cancer
75, 95–101 (2011).
et al. CD8+ tumor-infiltrating lymphocytes together with CD4+ tumor-infiltrating lymphocytes and dendritic cells improve the prognosis of patients with pancreatic adenocarcinoma. Pancreas
28, e26–e31 (2004).
De Monte, L.
et al. Intratumor T helper type 2 cell infiltrate correlates with cancer-associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer. J. Exp. Med.
208, 469–478 (2011).
et al. Carcinoembryonic antigen-specific but not antiviral CD4+ T cell immunity is impaired in pancreatic carcinoma patients. J. Immunol.
181, 6595–6603 (2008).
et al. IFN-γ produced by human papilloma virus-18 E6-specific CD4+ T cells predicts the clinical outcome after surgery in patients with high-grade cervical lesions. J. Immunol.
179, 7176–7183 (2007).
Cai, X. Y.
et al. Dendritic cell infiltration and prognosis of human hepatocellular carcinoma. J. Cancer Res. Clin. Oncol.
132, 293–301 (2006).
Wada, Y., Nakashima, O., Kutami, R., Yamamoto, O. & Kojiro, M.
Clinicopathological study on hepatocellular carcinoma with lymphocytic infiltration. Hepatology
27, 407–414 (1998).
et al. Tumor stroma reaction-related gene signature predicts clinical outcome in human hepatocellular carcinoma. Cancer Sci.
102, 1522–1531 (2011).
Zhang, J. P.
et al. Increased intratumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients. J. Hepatol.
50, 980–989 (2009).
Ubukata, H., Motohashi, G., Tabuchi, T., Nagata, H. & Konishi, S.
Evaluations of interferon-γ/interleukin-4 ratio and neutrophil/lymphocyte ratio as prognostic indicators in gastric cancer patients. J. Surg. Oncol.
102, 742–747 (2010).
Chen, J. G.
et al. Intratumoral expression of IL-17 and its prognostic role in gastric adenocarcinoma patients. Int. J. Biol. Sci.
7, 53–60 (2011).
et al. TH1 predominance is associated with improved survival in pediatric medulloblastoma patients. Cancer Immunol. Immunother.
60, 693–703 (2011).
Paulson, K. G.
et al. Transcriptome-wide studies of merkel cell carcinoma and validation of intratumoral CD8+ lymphocyte invasion as an independent predictor of survival. J. Clin. Oncol.
29, 1539–1546 (2011).