Skip to main content
Top
Published in: Cancer Immunology, Immunotherapy 12/2006

01-12-2006 | Original Article

Macrophage inflammatory protein (MIP)1α and MIP1β differentially regulate release of inflammatory cytokines and generation of tumoricidal monocytes in malignancy

Authors: Anamika Nath, Sreya Chattopadhya, Utpala Chattopadhyay, Nawal K. Sharma

Published in: Cancer Immunology, Immunotherapy | Issue 12/2006

Login to get access

Abstract

The C–C chemokines, macrophage inflammatory protein (MIP)1α and MIP1β are potent chemoattractants for the monocytes, which form an important component of the stroma of tumor tissue and may regulate tumor growth and associated inflammation. We examined the role of MIP1α and MIP1β in inducing the release of inflammatory cytokines and the generation of tumoricidal monocytes from the peripheral blood monocytes (PBM) of healthy women and patients with carcinoma of breast (CaBr). Interleukin-1 (IL-1) and tumor necrosis factor (TNF) α release by the PBM was markedly stimulated by MIP1α in CaBr patients, but only marginally so in healthy women. In contrast, MIP1β stimulated the release of these cytokines by the PBM of healthy women, but failed to do so in CaBr patients. MIP1α, but not MIP1β, synergized with LPS in inducing the release of IL-1 from the PBM of both healthy women and CaBr patients. Both MIP1α and MIP1β augmented respiratory bursts in PBM and generated tumoricidal PBM that killed T24 cells, MIP1α being more effective in CaBr patients and MIP1β in healthy women. IFN-γ co-stimulated and IL-4 suppressed MIP1α and β-induced cytotoxicity in PBM. The synergy of IFN-γ was more marked with MIP1α than with MIP1β. The differential effects of MIP1α and MIP1β on the PBM of healthy women and CaBr patients co-related with the levels of expression of CCR1 and CCR5 in these monocytes. The expression of CCR5 was higher than that of CCR1 in the PBM of healthy women and the PBM of the CaBr patients showed overexpression of CCR1 and downregulation of CCR5.
Literature
1.
go back to reference Asano T, An T, Jia SF, Kleinerman ES (1996) Altered monocyte chemotactic and activating factor gene expression in human glioblastoma cell lines increased their susceptibility to cytotoxicity. J Leukoc Biol 59:916PubMed Asano T, An T, Jia SF, Kleinerman ES (1996) Altered monocyte chemotactic and activating factor gene expression in human glioblastoma cell lines increased their susceptibility to cytotoxicity. J Leukoc Biol 59:916PubMed
2.
go back to reference Austrup F, Vestweber D, Borges E, Lohning M, Brauer R, Herz U, et al. (1997) P and E-selectin mediated recruitment of T helper 1 but not T helper 2 cells into inflamed tissues. Nature 385:81CrossRefPubMed Austrup F, Vestweber D, Borges E, Lohning M, Brauer R, Herz U, et al. (1997) P and E-selectin mediated recruitment of T helper 1 but not T helper 2 cells into inflamed tissues. Nature 385:81CrossRefPubMed
3.
go back to reference Baggiolini M, Dewald B, Moser B (1994) Interleukin-8 and related chemo tactic cytokines-CXC and CC chemokines. Adv Immunol 55:97PubMed Baggiolini M, Dewald B, Moser B (1994) Interleukin-8 and related chemo tactic cytokines-CXC and CC chemokines. Adv Immunol 55:97PubMed
4.
go back to reference Beckner SK (1997) G-protein activation by chemokines. Methods Enzymol 288:311 Beckner SK (1997) G-protein activation by chemokines. Methods Enzymol 288:311
5.
go back to reference Bellone G, Turletti A, Artusio E, Mareschi K, Carbone A, Tibandi D, et al. (1999) Tumor associated transforming growth factor beta and interleukin –10 contribute to a systemic TH-2 immune phenotype in pancreatic carcinoma patients. Am J Pathol 155:537PubMed Bellone G, Turletti A, Artusio E, Mareschi K, Carbone A, Tibandi D, et al. (1999) Tumor associated transforming growth factor beta and interleukin –10 contribute to a systemic TH-2 immune phenotype in pancreatic carcinoma patients. Am J Pathol 155:537PubMed
6.
go back to reference Chakraborty A, Chakrabarty NG, Chattopadhyay U (1996) Prolactin responses of NK cells but not of LAK cells is deficient in oral cancer patients. Int J Cancer 66:65CrossRefPubMed Chakraborty A, Chakrabarty NG, Chattopadhyay U (1996) Prolactin responses of NK cells but not of LAK cells is deficient in oral cancer patients. Int J Cancer 66:65CrossRefPubMed
7.
go back to reference Chattopadhyay U, Biswas R (2002) Prolactin regulates macrophage and NK cell mediated inflammation and cytotoxic response against tumor. In: Rapaport R, Matera L (eds) Growth and lactogenic hormone, vol 2. Neuroimmune biology Elsevier science. Amsterdam, p 227 Chattopadhyay U, Biswas R (2002) Prolactin regulates macrophage and NK cell mediated inflammation and cytotoxic response against tumor. In: Rapaport R, Matera L (eds) Growth and lactogenic hormone, vol 2. Neuroimmune biology Elsevier science. Amsterdam, p 227
8.
go back to reference Chensue SW, Ruth JH, Warmington K, Lincoln P, Kunkel SL (1995) In vivo regulation of macrophage IL-12 production during type 1 and type 2 cytokine mediated granuloma formation. J Immunol 155:3546PubMed Chensue SW, Ruth JH, Warmington K, Lincoln P, Kunkel SL (1995) In vivo regulation of macrophage IL-12 production during type 1 and type 2 cytokine mediated granuloma formation. J Immunol 155:3546PubMed
9.
go back to reference Cianciolo GJ, Hunter J, Silva J, Haskill JS, Snyderman R (1981) Inhibitors of monocyte responses to chemotaxins are present in human cancerous effusions and react with monoclonal antibodies to P15 (E) structural protein of retroviruses. J Clin Invest 68:831PubMedCrossRef Cianciolo GJ, Hunter J, Silva J, Haskill JS, Snyderman R (1981) Inhibitors of monocyte responses to chemotaxins are present in human cancerous effusions and react with monoclonal antibodies to P15 (E) structural protein of retroviruses. J Clin Invest 68:831PubMedCrossRef
10.
go back to reference Cohn ZA (1978) The activation of mononuclear phagocytes: fact, fancy and future. J Immunol 121:813PubMed Cohn ZA (1978) The activation of mononuclear phagocytes: fact, fancy and future. J Immunol 121:813PubMed
11.
go back to reference Conlon K, Llyod AR, Chattopadhyay U, Lucas N, Kunkel S, Schall T, et al. (1995) CD8+ and CD45RA+ human peripheral blood lymphocytes are potent source of macrophage inflammatory protein 1 alpha, IL-8 and RANTES. Eur J Immunol 25:751PubMedCrossRef Conlon K, Llyod AR, Chattopadhyay U, Lucas N, Kunkel S, Schall T, et al. (1995) CD8+ and CD45RA+ human peripheral blood lymphocytes are potent source of macrophage inflammatory protein 1 alpha, IL-8 and RANTES. Eur J Immunol 25:751PubMedCrossRef
12.
go back to reference Cox GW, Chattopadhyay U, Oppenheim JJ, Varesio L (1991) IL-4 inhibits the co-stimulatory activity of IL-2 or picolinic acid but not of lypopolysaccharide on IFN-γ treated macrophages. J Immunol 147:3809PubMed Cox GW, Chattopadhyay U, Oppenheim JJ, Varesio L (1991) IL-4 inhibits the co-stimulatory activity of IL-2 or picolinic acid but not of lypopolysaccharide on IFN-γ treated macrophages. J Immunol 147:3809PubMed
13.
go back to reference Decker T, Lohmann-Matthes MJ (1988) A quick and simple method for quantification of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J Immunol Methods 15:61CrossRef Decker T, Lohmann-Matthes MJ (1988) A quick and simple method for quantification of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J Immunol Methods 15:61CrossRef
14.
go back to reference Della-Rocca GJ, WanBiesen T, Daaka Y, Luttrell DK, Luttrell LM, Lefkowitz RJ (1997) Ras-dependent mitogen activated protein kinase activation by G protein coupled receptors. Convergence of Gi and Gq-mediated pathways on calcium/calmodulin, Pyk2 and Src kinase. J Biol Chem 272:19125CrossRefPubMed Della-Rocca GJ, WanBiesen T, Daaka Y, Luttrell DK, Luttrell LM, Lefkowitz RJ (1997) Ras-dependent mitogen activated protein kinase activation by G protein coupled receptors. Convergence of Gi and Gq-mediated pathways on calcium/calmodulin, Pyk2 and Src kinase. J Biol Chem 272:19125CrossRefPubMed
15.
go back to reference Dias S, Thomas H, Blackwell F (1998) Multiple molecular and cellular changes associated with tumor stasis and repression during IL-12 therapy of a murine breast cancer model. Int J Cancer 75:151CrossRefPubMed Dias S, Thomas H, Blackwell F (1998) Multiple molecular and cellular changes associated with tumor stasis and repression during IL-12 therapy of a murine breast cancer model. Int J Cancer 75:151CrossRefPubMed
16.
go back to reference Fahey TJ, Tracey KJ, Tekamp-Olson P, Cousens LS, Jones WG, Shires GT, et al. (1992) Macrophage inflammatory protein 1 modulates macrophage function. J Immunol 148:2764PubMed Fahey TJ, Tracey KJ, Tekamp-Olson P, Cousens LS, Jones WG, Shires GT, et al. (1992) Macrophage inflammatory protein 1 modulates macrophage function. J Immunol 148:2764PubMed
17.
go back to reference Flick DA, Gifford GE (1984) Comparision of invitro cell cytotoxic assays for tumor necrosis factor. J Immunol Methods 68:167CrossRefPubMed Flick DA, Gifford GE (1984) Comparision of invitro cell cytotoxic assays for tumor necrosis factor. J Immunol Methods 68:167CrossRefPubMed
18.
go back to reference Ganju RK, Dutt P, Wu L, Newman W, Avraham H, Avraham S, et al. (1998) Beta chemokine receptor CCR5 signals via the novel tyrosine kinase RAFTK. Blood 91:791PubMed Ganju RK, Dutt P, Wu L, Newman W, Avraham H, Avraham S, et al. (1998) Beta chemokine receptor CCR5 signals via the novel tyrosine kinase RAFTK. Blood 91:791PubMed
19.
go back to reference Han J, Lee JD, Bibbs L, Ulevitch RL (1994) A MAP kinase activation by endotoxin and hyperosmomolarity in mammalian cells. Science 265:808–811PubMedCrossRef Han J, Lee JD, Bibbs L, Ulevitch RL (1994) A MAP kinase activation by endotoxin and hyperosmomolarity in mammalian cells. Science 265:808–811PubMedCrossRef
20.
go back to reference Huang S, Singh RK, Xie K, Gutman M, Berry KK, Bucana CD, et al. (1994) Expression of JE/MCP-1 gene suppresses metastatic potential in murine colon carcinoma cells. Cancer Immunol Immunother 39:231CrossRefPubMed Huang S, Singh RK, Xie K, Gutman M, Berry KK, Bucana CD, et al. (1994) Expression of JE/MCP-1 gene suppresses metastatic potential in murine colon carcinoma cells. Cancer Immunol Immunother 39:231CrossRefPubMed
21.
go back to reference Jablonska E, Kiluk M, Piotrowski L, Grabowska Z, Markiewicz W, Jablonski J (1998) Tumor necrosis factor-alpha and soluble tumor necrosis factor receptors in the culture supernatants of polymorphonuclear cells and peripheral blood mononuclear cells from cancer patients. Eur Cytokine Netw 2:155 Jablonska E, Kiluk M, Piotrowski L, Grabowska Z, Markiewicz W, Jablonski J (1998) Tumor necrosis factor-alpha and soluble tumor necrosis factor receptors in the culture supernatants of polymorphonuclear cells and peripheral blood mononuclear cells from cancer patients. Eur Cytokine Netw 2:155
22.
go back to reference Jiang Y, Beller DI, Frendl G, Graves DT (1992) Monocyte chemoattractant protein-1 regulates adhesion molecule expression and cytokine production in human monocytes. J Immunol 148:2423PubMed Jiang Y, Beller DI, Frendl G, Graves DT (1992) Monocyte chemoattractant protein-1 regulates adhesion molecule expression and cytokine production in human monocytes. J Immunol 148:2423PubMed
23.
go back to reference Lee JC, Laydon JT, McDonnell PC, Gallagher TF, Kumar S, Green D, et al. (1994) A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature 372:739CrossRefPubMed Lee JC, Laydon JT, McDonnell PC, Gallagher TF, Kumar S, Green D, et al. (1994) A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature 372:739CrossRefPubMed
24.
go back to reference Loeffler CM, Smyth MJ, Longo DL, Kopp WC, Harvey LK, Tribble HR, et al. (1992) Immunoregulation in Cancer bearing hosts. Down-regulation of gene expression and cytotoxic function in CD8+ T cells. J Immunol 149:949PubMed Loeffler CM, Smyth MJ, Longo DL, Kopp WC, Harvey LK, Tribble HR, et al. (1992) Immunoregulation in Cancer bearing hosts. Down-regulation of gene expression and cytotoxic function in CD8+ T cells. J Immunol 149:949PubMed
25.
go back to reference Mantovani A, Bottazzi B, Collotta F, Sozzani S, Ruco L (1992) The origin and function of tumor associated macrophages. Immunol Today 13:265CrossRefPubMed Mantovani A, Bottazzi B, Collotta F, Sozzani S, Ruco L (1992) The origin and function of tumor associated macrophages. Immunol Today 13:265CrossRefPubMed
26.
go back to reference Mantovani A, Vecchi A, Sozzani S, Sica A, Allavena P (1999) Tumors as a paradigm for the invivo role of chemokines in leukocytes recruitment. In: Rollins BJ (eds) Chemokines and cancer. Humana press, Totowa, NJ, p 35 Mantovani A, Vecchi A, Sozzani S, Sica A, Allavena P (1999) Tumors as a paradigm for the invivo role of chemokines in leukocytes recruitment. In: Rollins BJ (eds) Chemokines and cancer. Humana press, Totowa, NJ, p 35
27.
go back to reference Miller MD, Krangel MS (1992) Biology and biochemistry of the chemokines: a family of chemotactic and inflammatory cytokines. Crit Rev Immunol 12:17PubMed Miller MD, Krangel MS (1992) Biology and biochemistry of the chemokines: a family of chemotactic and inflammatory cytokines. Crit Rev Immunol 12:17PubMed
28.
go back to reference Mizel SB, Oppemheim JJ, Rosenstreich DL (1978) Characterization of lymphocyte activating factor (LAF) produced by macrophage cell line P388D1. I. Enhancement of LAF production by activated T lymphocytes. J Immunol 120:1497PubMed Mizel SB, Oppemheim JJ, Rosenstreich DL (1978) Characterization of lymphocyte activating factor (LAF) produced by macrophage cell line P388D1. I. Enhancement of LAF production by activated T lymphocytes. J Immunol 120:1497PubMed
29.
go back to reference Mossman T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assay. J Immunol Methods 65:55CrossRefPubMed Mossman T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assay. J Immunol Methods 65:55CrossRefPubMed
30.
go back to reference Nishioka Y, Sone S, Orino Nii A, Ogura T (1991) Down regulation by interleukin-4 of activation of human alveolar macrophages to the tumoricidal state. Cancer Res 51:5526PubMed Nishioka Y, Sone S, Orino Nii A, Ogura T (1991) Down regulation by interleukin-4 of activation of human alveolar macrophages to the tumoricidal state. Cancer Res 51:5526PubMed
31.
go back to reference Opdenakker G, Van Damme J (1992) Cytokines and proteases in invasive process: molecular similarities between inflammation and cancer. Cytokine 4:251CrossRefPubMed Opdenakker G, Van Damme J (1992) Cytokines and proteases in invasive process: molecular similarities between inflammation and cancer. Cytokine 4:251CrossRefPubMed
32.
go back to reference Oppenheim JJ, Zachariae OC, Mukaida N, Matsushima K (1991) Properties of the novel proinflammatory supergene “Intercrine” cytokine family. Annu Rev Immunol 9:617PubMed Oppenheim JJ, Zachariae OC, Mukaida N, Matsushima K (1991) Properties of the novel proinflammatory supergene “Intercrine” cytokine family. Annu Rev Immunol 9:617PubMed
33.
go back to reference Pike E, Mizel D (1981) Rapid microassay for the measurement of superoxide and hydrogen peroxide production by macrophages in culture using an automatic immunoassay reader. J Immunol Methods 46:211CrossRefPubMed Pike E, Mizel D (1981) Rapid microassay for the measurement of superoxide and hydrogen peroxide production by macrophages in culture using an automatic immunoassay reader. J Immunol Methods 46:211CrossRefPubMed
34.
go back to reference Pohlman TH, Stanness KA, Beatty PG, Ochs HD, Harlan JM (1986) An endothelial cell surface factor(s) induced in vitro by LPS, IL-1 and TNF-alpha increases neutrophil adherence by a CDW18-dependent mechanism. J Immunol 136:4548PubMed Pohlman TH, Stanness KA, Beatty PG, Ochs HD, Harlan JM (1986) An endothelial cell surface factor(s) induced in vitro by LPS, IL-1 and TNF-alpha increases neutrophil adherence by a CDW18-dependent mechanism. J Immunol 136:4548PubMed
35.
go back to reference Sallusto F, Lanzavecchia A, Mackay CR (1998) Chemokines and chemokine receptors in T-cell priming and Th-1/Th-2 mediated responses. Immunol Today 19:568–574CrossRefPubMed Sallusto F, Lanzavecchia A, Mackay CR (1998) Chemokines and chemokine receptors in T-cell priming and Th-1/Th-2 mediated responses. Immunol Today 19:568–574CrossRefPubMed
36.
go back to reference Schrum S, Probst P, Fleischer B, Zipfel PF (1996) Synthesis of the C–C chemokines MIP1α, MIP1β and RANTES are associated with a type 1 immune response. J Immunol 157:3598PubMed Schrum S, Probst P, Fleischer B, Zipfel PF (1996) Synthesis of the C–C chemokines MIP1α, MIP1β and RANTES are associated with a type 1 immune response. J Immunol 157:3598PubMed
37.
go back to reference Selvan RS, Kapadia HB, Platt JL (1998) Complement induced expression of chemokine genes in endothelium: regulation by IL-1 dependent mechanisms. J Immunol 161:4388PubMed Selvan RS, Kapadia HB, Platt JL (1998) Complement induced expression of chemokine genes in endothelium: regulation by IL-1 dependent mechanisms. J Immunol 161:4388PubMed
38.
go back to reference Singh RK, Berry K, Matsushima K, Yasumoto K, Fidler IJ (1993) Synergism between human monocyte chemotactic and activating factor and bacterial products for activation of tumoricidal property of murine macrophages. J Immunol 151:2786PubMed Singh RK, Berry K, Matsushima K, Yasumoto K, Fidler IJ (1993) Synergism between human monocyte chemotactic and activating factor and bacterial products for activation of tumoricidal property of murine macrophages. J Immunol 151:2786PubMed
39.
go back to reference Siveke JT, Hamann A (1998) Cutting edge: T helper 1 and T helper 2 cells responds differentially to chemokines. J Immunol 160:550PubMed Siveke JT, Hamann A (1998) Cutting edge: T helper 1 and T helper 2 cells responds differentially to chemokines. J Immunol 160:550PubMed
40.
go back to reference Taub DD, Conlon K, Lloyd AR, Oppenheim JJ, Kelvin DJ (1993) Preferential migration of activated CD4+ and CD8+ T cells in response to MIP1α and MIP1β?. Science 260:355PubMedCrossRef Taub DD, Conlon K, Lloyd AR, Oppenheim JJ, Kelvin DJ (1993) Preferential migration of activated CD4+ and CD8+ T cells in response to MIP1α and MIP1β?. Science 260:355PubMedCrossRef
41.
go back to reference Taub DD (1999) Natural killer-cell-chemokine interactions. In: Rollins BJ (eds) Chemokines and Cancer. Humana press, Totowa, NJ, p 35 Taub DD (1999) Natural killer-cell-chemokine interactions. In: Rollins BJ (eds) Chemokines and Cancer. Humana press, Totowa, NJ, p 35
42.
go back to reference Wang JM, Chertov O, Proost P, Li JJ, Menten P, Xu L, et al. (1998) Purification and identification of chemokines potentially involved in kidney-specific metastasis by a murine lymphoma variant: induction of migration and NF kβ activation. Int J Cancer 75:900CrossRefPubMed Wang JM, Chertov O, Proost P, Li JJ, Menten P, Xu L, et al. (1998) Purification and identification of chemokines potentially involved in kidney-specific metastasis by a murine lymphoma variant: induction of migration and NF kβ activation. Int J Cancer 75:900CrossRefPubMed
43.
go back to reference Wang JM, Deng X, Gong W, Su S (1998) Chemokines and their role in tumor growth and metastasis. J Immunol Methods 220:1CrossRefPubMed Wang JM, Deng X, Gong W, Su S (1998) Chemokines and their role in tumor growth and metastasis. J Immunol Methods 220:1CrossRefPubMed
44.
go back to reference Wang JM, Shen W, Chertov O, Van Damme J, Oppenheim J (1999) Chemokine modulation of tumor cell physiology. In: Rollins BJ (eds) Chemokines and Cancer, Humana Press, Totowa, NJ, p 129 Wang JM, Shen W, Chertov O, Van Damme J, Oppenheim J (1999) Chemokine modulation of tumor cell physiology. In: Rollins BJ (eds) Chemokines and Cancer, Humana Press, Totowa, NJ, p 129
45.
go back to reference Wiltrout RH, Varesio L (1990) Activation of macrophage for cytotoxic and suppressor effector functions. In: Oppenhein JJ, Shevarch EM (eds) Immunophysiology. The role of cells and cytokines in immunity and inflammation. Oxford University press, NY, pp365 Wiltrout RH, Varesio L (1990) Activation of macrophage for cytotoxic and suppressor effector functions. In: Oppenhein JJ, Shevarch EM (eds) Immunophysiology. The role of cells and cytokines in immunity and inflammation. Oxford University press, NY, pp365
46.
go back to reference Zachariae CO, Anderson AO, Thompson HL, Apella E, Mantovani A, Oppenheim JJ, et al. (1990) Properties of monocyte chemotactic and activating factor (MCAF) purified from a human fibrosarcoma cell line. J Exp Med 171:2177CrossRefPubMed Zachariae CO, Anderson AO, Thompson HL, Apella E, Mantovani A, Oppenheim JJ, et al. (1990) Properties of monocyte chemotactic and activating factor (MCAF) purified from a human fibrosarcoma cell line. J Exp Med 171:2177CrossRefPubMed
47.
go back to reference Zella D, Barabitskaja O, Burns JM, Romerio F, Dunn DE, Revello MG, et al. (1998) Interferon γ increases expression of chemokine receptors CCR1, CCR3 and CCR5, but not CXCR4 in monocytoid U937 cells. Blood 91:4444PubMed Zella D, Barabitskaja O, Burns JM, Romerio F, Dunn DE, Revello MG, et al. (1998) Interferon γ increases expression of chemokine receptors CCR1, CCR3 and CCR5, but not CXCR4 in monocytoid U937 cells. Blood 91:4444PubMed
Metadata
Title
Macrophage inflammatory protein (MIP)1α and MIP1β differentially regulate release of inflammatory cytokines and generation of tumoricidal monocytes in malignancy
Authors
Anamika Nath
Sreya Chattopadhya
Utpala Chattopadhyay
Nawal K. Sharma
Publication date
01-12-2006
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 12/2006
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-006-0149-3

Other articles of this Issue 12/2006

Cancer Immunology, Immunotherapy 12/2006 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