Gemcitabine exerts a selective effect on the humoral immune response: implications for combination chemo-immunotherapy

AK Nowak, BWS Robinson, RA Lake - Cancer research, 2002 - AACR
Cancer research, 2002AACR
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+ …
Abstract
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.
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