Skip to main content
Top
Published in: Cancer Cell International 1/2011

Open Access 01-12-2011 | Primary research

Novel innate cancer killing activity in humans

Authors: Michael J Blanks, John R Stehle Jr, Wei Du, Jonathan M Adams, Mark C Willingham, Glenn O Allen, Jennifer J Hu, James Lovato, Istvan Molnar, Zheng Cui

Published in: Cancer Cell International | Issue 1/2011

Login to get access

Abstract

Background

In this study, we pilot tested an in vitro assay of cancer killing activity (CKA) in circulating leukocytes of 22 cancer cases and 25 healthy controls.

Methods

Using a human cervical cancer cell line, HeLa, as target cells, we compared the CKA in circulating leukocytes, as effector cells, of cancer cases and controls. The CKA was normalized as percentages of total target cells during selected periods of incubation time and at selected effector/target cell ratios in comparison to no-effector-cell controls.

Results

Our results showed that CKA similar to that of our previous study of SR/CR mice was present in human circulating leukocytes but at profoundly different levels in individuals. Overall, males have a significantly higher CKA than females. The CKA levels in cancer cases were lower than that in healthy controls (mean ± SD: 36.97 ± 21.39 vs. 46.28 ± 27.22). Below-median CKA was significantly associated with case status (odds ratio = 4.36; 95% Confidence Interval = 1.06, 17.88) after adjustment of gender and race.

Conclusions

In freshly isolated human leukocytes, we were able to detect an apparent CKA in a similar manner to that of cancer-resistant SR/CR mice. The finding of CKA at lower levels in cancer patients suggests the possibility that it may be of a consequence of genetic, physiological, or pathological conditions, pending future studies with larger sample size.
Appendix
Available only for authorised users
Literature
1.
go back to reference Ehrlich P: Ueber den jetzigen Stand der Karzinomforschung. Ned Tijdschr Geneeskd. 1909, 5: 273-290. Ehrlich P: Ueber den jetzigen Stand der Karzinomforschung. Ned Tijdschr Geneeskd. 1909, 5: 273-290.
4.
go back to reference Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD: Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002, 3 (11): 991-998. 10.1038/ni1102-991.CrossRefPubMed Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD: Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002, 3 (11): 991-998. 10.1038/ni1102-991.CrossRefPubMed
5.
go back to reference Cui Z, Willingham MC, Hicks AM, Alexander-Miller MA, Howard TD, Hawkins GA, Miller MS, Weir HM, Du W, DeLong CJ: Spontaneous regression of advanced cancer: identification of a unique genetically determined, age-dependent trait in mice. Proc Natl Acad Sci USA. 2003, 100 (11): 6682-6687. 10.1073/pnas.1031601100.PubMedCentralCrossRefPubMed Cui Z, Willingham MC, Hicks AM, Alexander-Miller MA, Howard TD, Hawkins GA, Miller MS, Weir HM, Du W, DeLong CJ: Spontaneous regression of advanced cancer: identification of a unique genetically determined, age-dependent trait in mice. Proc Natl Acad Sci USA. 2003, 100 (11): 6682-6687. 10.1073/pnas.1031601100.PubMedCentralCrossRefPubMed
6.
go back to reference Kloss S, Bochennek K, Huenecke S, Zimmermann S, Kuci S, Muller T, Wels W, Klingebiel T, Esser R, Koehl U: A novel five-colour flow cytometric assay to determine NK cell cytotoxicity against neuroblastoma and other adherent tumour cells. J Immunol Methods. 2007, 325 (1-2): 140-147. 10.1016/j.jim.2007.06.013.CrossRefPubMed Kloss S, Bochennek K, Huenecke S, Zimmermann S, Kuci S, Muller T, Wels W, Klingebiel T, Esser R, Koehl U: A novel five-colour flow cytometric assay to determine NK cell cytotoxicity against neuroblastoma and other adherent tumour cells. J Immunol Methods. 2007, 325 (1-2): 140-147. 10.1016/j.jim.2007.06.013.CrossRefPubMed
7.
go back to reference Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K: Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet. 2000, 356 (9244): 1795-1799. 10.1016/S0140-6736(00)03231-1.CrossRefPubMed Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K: Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet. 2000, 356 (9244): 1795-1799. 10.1016/S0140-6736(00)03231-1.CrossRefPubMed
8.
go back to reference Kim G, Donnenberg V, Donnenberg A, Gooding W, Whiteside T: A novel multiparametric flow cytometry-based cytotoxicity assay simultaneously immunophenotypes effector cells: comparisons to a 4 h 51Cr-release assay. J Immunol Methods. 2007, 325 (1-2): 51-66. 10.1016/j.jim.2007.05.013.PubMedCentralCrossRefPubMed Kim G, Donnenberg V, Donnenberg A, Gooding W, Whiteside T: A novel multiparametric flow cytometry-based cytotoxicity assay simultaneously immunophenotypes effector cells: comparisons to a 4 h 51Cr-release assay. J Immunol Methods. 2007, 325 (1-2): 51-66. 10.1016/j.jim.2007.05.013.PubMedCentralCrossRefPubMed
9.
go back to reference Langhans B, Ahrendt M, Nattermann J, Sauerbruch T, Spengler U: Comparative study of NK cell-mediated cytotoxicity using radioactive and flow cytometric cytotoxicity assays. J Immunol Methods. 2005, 306 (1-2): 161-168. 10.1016/j.jim.2005.08.010.CrossRefPubMed Langhans B, Ahrendt M, Nattermann J, Sauerbruch T, Spengler U: Comparative study of NK cell-mediated cytotoxicity using radioactive and flow cytometric cytotoxicity assays. J Immunol Methods. 2005, 306 (1-2): 161-168. 10.1016/j.jim.2005.08.010.CrossRefPubMed
10.
go back to reference Strayer DR, Carter WA, Mayberry SD, Pequignot E, Brodsky I: Low natural cytotoxicity of peripheral blood mononuclear cells in individuals with high familial incidences of cancer. Cancer Res. 1984, 44 (1): 370-374.PubMed Strayer DR, Carter WA, Mayberry SD, Pequignot E, Brodsky I: Low natural cytotoxicity of peripheral blood mononuclear cells in individuals with high familial incidences of cancer. Cancer Res. 1984, 44 (1): 370-374.PubMed
11.
go back to reference Hicks AM, Riedlinger G, Willingham MC, Alexander-Miller MA, Von Kap-Herr C, Pettenati MJ, Sanders AM, Weir HM, Du W, Kim J: Transferable anticancer innate immunity in spontaneous regression/complete resistance mice. Proc Natl Acad Sci USA. 2006, 103 (20): 7753-7758. 10.1073/pnas.0602382103.PubMedCentralCrossRefPubMed Hicks AM, Riedlinger G, Willingham MC, Alexander-Miller MA, Von Kap-Herr C, Pettenati MJ, Sanders AM, Weir HM, Du W, Kim J: Transferable anticancer innate immunity in spontaneous regression/complete resistance mice. Proc Natl Acad Sci USA. 2006, 103 (20): 7753-7758. 10.1073/pnas.0602382103.PubMedCentralCrossRefPubMed
12.
go back to reference Sanders A: Characterization of the inheritance, effector mechanisms, and response against endogenous cancers in the SR/CR mouse model of cancer resistance. 2007, Winston-Salem: Wake Forest University Graduate School of Arts and Sciences Sanders A: Characterization of the inheritance, effector mechanisms, and response against endogenous cancers in the SR/CR mouse model of cancer resistance. 2007, Winston-Salem: Wake Forest University Graduate School of Arts and Sciences
13.
go back to reference Riedlinger G, Adams J, Stehle JR, Blanks MJ, Sanders AM, Hicks AM, Willingham MC, Cui Z: The spectrum of resistance in SR/CR mice: the critical role of chemoattraction in the cancer/leukocyte interaction. BMC Cancer. 2010, 10 (1): 179-10.1186/1471-2407-10-179.PubMedCentralCrossRefPubMed Riedlinger G, Adams J, Stehle JR, Blanks MJ, Sanders AM, Hicks AM, Willingham MC, Cui Z: The spectrum of resistance in SR/CR mice: the critical role of chemoattraction in the cancer/leukocyte interaction. BMC Cancer. 2010, 10 (1): 179-10.1186/1471-2407-10-179.PubMedCentralCrossRefPubMed
14.
go back to reference Southam CM: Emotions, immunology, and cancer: how might the psyche influence neoplasia?. Ann N Y Acad Sci. 1969, 164 (2): 473-475. 10.1111/j.1749-6632.1969.tb14063.x.CrossRefPubMed Southam CM: Emotions, immunology, and cancer: how might the psyche influence neoplasia?. Ann N Y Acad Sci. 1969, 164 (2): 473-475. 10.1111/j.1749-6632.1969.tb14063.x.CrossRefPubMed
15.
go back to reference van Rood Y, Goulmy E, Blokland E, Pool J, van Rood J, van Houwelingen H: Month-related variability in immunological test results; implications for immunological follow-up studies. Clin Exp Immunol. 1991, 86 (2): 349-354.PubMedCentralCrossRefPubMed van Rood Y, Goulmy E, Blokland E, Pool J, van Rood J, van Houwelingen H: Month-related variability in immunological test results; implications for immunological follow-up studies. Clin Exp Immunol. 1991, 86 (2): 349-354.PubMedCentralCrossRefPubMed
16.
go back to reference Armario A, Marti O, Molina T, de Pablo J, Valdes M: Acute stress markers in humans: response of plasma glucose, cortisol and prolactin to two examinations differing in the anxiety they provoke. Psychoneuroendocrinology. 1996, 21 (1): 17-24. 10.1016/0306-4530(95)00048-8.CrossRefPubMed Armario A, Marti O, Molina T, de Pablo J, Valdes M: Acute stress markers in humans: response of plasma glucose, cortisol and prolactin to two examinations differing in the anxiety they provoke. Psychoneuroendocrinology. 1996, 21 (1): 17-24. 10.1016/0306-4530(95)00048-8.CrossRefPubMed
17.
go back to reference Nelson RJ, Demas GE, Klein SL, Kriegsfeld LJ: Seasonal Patterns of Stress, Immune Function, & Disease. 2002, Cambridge University PressCrossRef Nelson RJ, Demas GE, Klein SL, Kriegsfeld LJ: Seasonal Patterns of Stress, Immune Function, & Disease. 2002, Cambridge University PressCrossRef
18.
go back to reference Nelson R, Demas G, Kriegsfeld L: Seasonal Patterns of Stress, Immune Function, & Disease. 2002CrossRef Nelson R, Demas G, Kriegsfeld L: Seasonal Patterns of Stress, Immune Function, & Disease. 2002CrossRef
19.
go back to reference Edwards BK, Ward E, Kohler BA, Eheman C, Zauber AG, Anderson RN, Jemal A, Schymura MJ, Lansdorp-Vogelaar I, Seeff LC: Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer. 2010, 116 (3): 544-573. 10.1002/cncr.24760.PubMedCentralCrossRefPubMed Edwards BK, Ward E, Kohler BA, Eheman C, Zauber AG, Anderson RN, Jemal A, Schymura MJ, Lansdorp-Vogelaar I, Seeff LC: Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer. 2010, 116 (3): 544-573. 10.1002/cncr.24760.PubMedCentralCrossRefPubMed
20.
go back to reference Brawley OW: Population categorization and cancer statistics. Cancer Metastasis Rev. 2003, 22 (1): 11-19. 10.1023/A:1022244618834.CrossRefPubMed Brawley OW: Population categorization and cancer statistics. Cancer Metastasis Rev. 2003, 22 (1): 11-19. 10.1023/A:1022244618834.CrossRefPubMed
21.
go back to reference Fish EN: The X-files in immunity: sex-based differences predispose immune responses. Nat Rev Immunol. 2008, 8 (9): 737-744. 10.1038/nri2394.CrossRefPubMed Fish EN: The X-files in immunity: sex-based differences predispose immune responses. Nat Rev Immunol. 2008, 8 (9): 737-744. 10.1038/nri2394.CrossRefPubMed
22.
go back to reference Nilsson N, Carlsten H: Estrogen induces suppression of natural killer cell cytotoxicity and augmentation of polyclonal B cell activation. Cell Immunol. 1994, 158 (1): 131-139. 10.1006/cimm.1994.1262.CrossRefPubMed Nilsson N, Carlsten H: Estrogen induces suppression of natural killer cell cytotoxicity and augmentation of polyclonal B cell activation. Cell Immunol. 1994, 158 (1): 131-139. 10.1006/cimm.1994.1262.CrossRefPubMed
23.
go back to reference Harkonen PL, Vaananen HK: Monocyte-macrophage system as a target for estrogen and selective estrogen receptor modulators. Ann N Y Acad Sci. 2006, 1089: 218-227. 10.1196/annals.1386.045.CrossRefPubMed Harkonen PL, Vaananen HK: Monocyte-macrophage system as a target for estrogen and selective estrogen receptor modulators. Ann N Y Acad Sci. 2006, 1089: 218-227. 10.1196/annals.1386.045.CrossRefPubMed
24.
go back to reference Cui Z: The winding road to the discovery of the SR/CR mice. Cancer Immun. 2003, 3: 14-PubMed Cui Z: The winding road to the discovery of the SR/CR mice. Cancer Immun. 2003, 3: 14-PubMed
25.
go back to reference Cui Z, Willingham M: The effect of aging on cellular immunity against cancer in SR/CR mice. Cancer Immunol Immunother. 2004, 53 (6): 473-478. 10.1007/s00262-003-0488-2.CrossRefPubMed Cui Z, Willingham M: The effect of aging on cellular immunity against cancer in SR/CR mice. Cancer Immunol Immunother. 2004, 53 (6): 473-478. 10.1007/s00262-003-0488-2.CrossRefPubMed
26.
go back to reference Hicks A, Willingham M, Du W, Pang C, Old L, Cui Z: Effector mechanisms of the anti-cancer immune responses of macrophages in SR/CR mice. Cancer Immun. 2006, 6: 11-PubMed Hicks A, Willingham M, Du W, Pang C, Old L, Cui Z: Effector mechanisms of the anti-cancer immune responses of macrophages in SR/CR mice. Cancer Immun. 2006, 6: 11-PubMed
27.
go back to reference Stehle JR, Blanks MJ, Riedlinger G, Kim-Shapiro JW, Sanders AM, Adams JM, Willingham MC, Cui Z: Impact of sex, MHC, and age of recipients on the therapeutic effect of transferred leukocytes from cancer-resistant SR/CR mice. BMC Cancer. 2009, 9: 328-10.1186/1471-2407-9-328.PubMedCentralCrossRefPubMed Stehle JR, Blanks MJ, Riedlinger G, Kim-Shapiro JW, Sanders AM, Adams JM, Willingham MC, Cui Z: Impact of sex, MHC, and age of recipients on the therapeutic effect of transferred leukocytes from cancer-resistant SR/CR mice. BMC Cancer. 2009, 9: 328-10.1186/1471-2407-9-328.PubMedCentralCrossRefPubMed
28.
go back to reference Perera FP: Molecular epidemiology: insights into cancer susceptibility, risk assessment, and prevention. J Natl Cancer Inst. 1996, 88 (8): 496-509. 10.1093/jnci/88.8.496.CrossRefPubMed Perera FP: Molecular epidemiology: insights into cancer susceptibility, risk assessment, and prevention. J Natl Cancer Inst. 1996, 88 (8): 496-509. 10.1093/jnci/88.8.496.CrossRefPubMed
29.
go back to reference Shibata A, Whittemore AS: Genetic predisposition to prostate cancer: possible explanations for ethnic differences in risk. Prostate. 1997, 32 (1): 65-72. 10.1002/(SICI)1097-0045(19970615)32:1<65::AID-PROS9>3.0.CO;2-B.CrossRefPubMed Shibata A, Whittemore AS: Genetic predisposition to prostate cancer: possible explanations for ethnic differences in risk. Prostate. 1997, 32 (1): 65-72. 10.1002/(SICI)1097-0045(19970615)32:1<65::AID-PROS9>3.0.CO;2-B.CrossRefPubMed
Metadata
Title
Novel innate cancer killing activity in humans
Authors
Michael J Blanks
John R Stehle Jr
Wei Du
Jonathan M Adams
Mark C Willingham
Glenn O Allen
Jennifer J Hu
James Lovato
Istvan Molnar
Zheng Cui
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2011
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-11-26

Other articles of this Issue 1/2011

Cancer Cell International 1/2011 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine