This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nowak, A. K. Articles by Lake, R. A. Search for Related Content PubMed PubMed Citation Articles by Nowak, A. K. Articles by Lake, R. A.

Gemcitabine Exerts a Selective Effect on the Humoral Immune Response

Implications for Combination Chemo-immunotherapy¹

Western Australian Institute for Medical Research University Department of Medicine, Queen Elizabeth II Medical Centre, Perth, Western Australia 6009

Most cytotoxic drugs have gross effects on the immune system, such as neutropenia and lymphopenia. However, their effects on tumor-specific immune responses are unknown. Gemcitabine is a nucleoside analogue that is frequently used to treat non-small cell lung cancer. It is also active in other malignancies, either alone or in combination with cisplatin. Here, we investigate its effects on antigen-specific antitumor immunity using a murine tumor cell line transfected to express influenza virus hemagglutinin (HA). CD4⁺, CD8⁺, and B220⁺ lymphocyte numbers all decreased during chemotherapy (120 µg/g, i.p., every third day for five doses), but B cells were selectively depleted. Gemcitabine induced a profound suppression of the IgG antibody response to HA, and this was unrelated to tumor size. In contrast, in vitro T-lymphocyte recall responses to the class I- and class II-restricted dominant peptide epitopes of HA were enhanced in tumor-bearing, gemcitabine-treated mice. We found that gemcitabine was >2-fold more potent in its ability to inhibit B-lymphocyte proliferation compared with T-lymphocyte proliferation. Thus, gemcitabine does not appear to be detrimental to specific antitumor cellular immunity and may be useful in combination chemo-immunotherapy protocols. In contrast, vaccination protocols requiring a humoral immune response for maximal efficacy may be compromised in patients treated with gemcitabine.

This article has been cited by other articles:

				A. Soeda, Y. Morita-Hoshi, H. Makiyama, C. Morizane, H. Ueno, M. Ikeda, T. Okusaka, S. Yamagata, N. Takahashi, I. Hyodo, et al. Regular Dose of Gemcitabine Induces an Increase in CD14+ Monocytes and CD11c+ Dendritic Cells in Patients with Advanced Pancreatic Cancer Jpn. J. Clin. Oncol., December 1, 2009; 39(12): 797 - 806. [Abstract] [Full Text] [PDF]

				H. Tanaka, H. Matsushima, A. Nishibu, B. E. Clausen, and A. Takashima Dual Therapeutic Efficacy of Vinblastine as a Unique Chemotherapeutic Agent Capable of Inducing Dendritic Cell Maturation Cancer Res., September 1, 2009; 69(17): 6987 - 6994. [Abstract] [Full Text] [PDF]

				A. L. Angelova, M. Aprahamian, S. P. Grekova, A. Hajri, B. Leuchs, N. A. Giese, C. Dinsart, A. Herrmann, G. Balboni, J. Rommelaere, et al. Improvement of Gemcitabine-Based Therapy of Pancreatic Carcinoma by Means of Oncolytic Parvovirus H-1PV Clin. Cancer Res., January 15, 2009; 15(2): 511 - 519. [Abstract] [Full Text] [PDF]

				C Bauer, F Bauernfeind, A Sterzik, M Orban, M Schnurr, H A Lehr, S Endres, A Eigler, and M Dauer Dendritic cell-based vaccination combined with gemcitabine increases survival in a murine pancreatic carcinoma model Gut, September 1, 2007; 56(9): 1275 - 1282. [Abstract] [Full Text] [PDF]

				M. Lucchi, A. Chella, F. Melfi, P. Dini, M. Ambrogi, L. Fino, G. Fontanini, and A. Mussi A phase II study of intrapleural immuno-chemotherapy, pleurectomy/decortication, radiotherapy, systemic chemotherapy and long-term sub-cutaneous IL-2 in stage II-III malignant pleural mesothelioma Eur. J. Cardiothorac. Surg., March 1, 2007; 31(3): 529 - 534. [Abstract] [Full Text] [PDF]

				A. L Sommer, B. K Wachel, and J. A Smith Evaluation of vaccine dosing in patients with solid tumors receiving myelosuppressive chemotherapy Journal of Oncology Pharmacy Practice, September 1, 2006; 12(3): 143 - 154. [Abstract] [PDF]

				K. Kimura, T. Sawada, M. Komatsu, M. Inoue, K. Muguruma, T. Nishihara, Y. Yamashita, N. Yamada, M. Ohira, and K. Hirakawa Antitumor Effect of Trastuzumab for Pancreatic Cancer with High HER-2 Expression and Enhancement of Effect by Combined Therapy with Gemcitabine. Clin. Cancer Res., August 15, 2006; 12(16): 4925 - 4932. [Abstract] [Full Text] [PDF]

				P. Correale, M. G. Cusi, K. Y. Tsang, M. T. Del Vecchio, S. Marsili, M. L. Placa, C. Intrivici, A. Aquino, L. Micheli, C. Nencini, et al. Chemo-Immunotherapy of Metastatic Colorectal Carcinoma With Gemcitabine Plus FOLFOX 4 Followed by Subcutaneous Granulocyte Macrophage Colony-Stimulating Factor and Interleukin-2 Induces Strong Immunologic and Antitumor Activity in Metastatic Colon Cancer Patients J. Clin. Oncol., December 10, 2005; 23(35): 8950 - 8958. [Abstract] [Full Text] [PDF]

				L. A. Emens and E. M. Jaffee Leveraging the Activity of Tumor Vaccines with Cytotoxic Chemotherapy Cancer Res., September 15, 2005; 65(18): 8059 - 8064. [Abstract] [Full Text] [PDF]

				E. Suzuki, V. Kapoor, A. S. Jassar, L. R. Kaiser, and S. M. Albelda Gemcitabine Selectively Eliminates Splenic Gr-1+/CD11b+ Myeloid Suppressor Cells in Tumor-Bearing Animals and Enhances Antitumor Immune Activity Clin. Cancer Res., September 15, 2005; 11(18): 6713 - 6721. [Abstract] [Full Text] [PDF]

				S. Broomfield, A. Currie, R. G. van der Most, M. Brown, I. van Bruggen, B. W.S. Robinson, and R. A. Lake Partial, but not Complete, Tumor-Debulking Surgery Promotes Protective Antitumor Memory when Combined with Chemotherapy and Adjuvant Immunotherapy Cancer Res., September 1, 2005; 65(17): 7580 - 7584. [Abstract] [Full Text] [PDF]

				P. Correale*, M. G. Cusi, M. T. Del Vecchio, A. Aquino, S. Prete, K. Y. Tsang, L. Micheli, C. Nencini, M. La Placa*, F. Montagnani*, et al. Dendritic Cell-Mediated Cross-Presentation of Antigens Derived from Colon Carcinoma Cells Exposed to a Highly Cytotoxic Multidrug Regimen with Gemcitabine, Oxaliplatin, 5-Fluorouracil, and Leucovorin, Elicits a Powerful Human Antigen-Specific CTL Response with Antitumor Activity in Vitro J. Immunol., July 15, 2005; 175(2): 820 - 828. [Abstract] [Full Text] [PDF]

				A. K. Nowak, B. W. S. Robinson, and R. A. Lake Synergy between Chemotherapy and Immunotherapy in the Treatment of Established Murine Solid Tumors Cancer Res., August 1, 2003; 63(15): 4490 - 4496. [Abstract] [Full Text] [PDF]

				A. K. Nowak, R. A. Lake, A. L. Marzo, B. Scott, W. R. Heath, E. J. Collins, J. A. Frelinger, and B. W. S. Robinson Induction of Tumor Cell Apoptosis In Vivo Increases Tumor Antigen Cross-Presentation, Cross-Priming Rather than Cross-Tolerizing Host Tumor-Specific CD8 T Cells J. Immunol., May 15, 2003; 170(10): 4905 - 4913. [Abstract] [Full Text] [PDF]