PubMed · 12127875
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Steven M Holland, E Sylvester Vizi. 2002. Immunomodulation.. https://doi.org/10.1016/s1471-4892(02)00188-1
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Bacterial DNA and synthetic oligodeoxynucleotides containing CpG motifs (CpG-ODNs) are strong activators of both innate and specific immunity, driving the immune response towards the Th1 phenotype. CpG-ODNs have been successfully used in several experimental models of allergies or infections and are now entering clinical trials for these diseases. In this review, we will focus on their potential applications in cancers. CpG-ODN can be used alone to activate locally the innate immunity and trigger a tumor-specific immune response, overcoming the need for identification of a relevant tumoral antigen. Other promising approaches combined CpG-ODN with tumor antigens, monoclonal antibodies or dendritic cells. Preclinical models have shown impressive results and several clinical trials are on-going worldwide. So far, the toxicity observed in humans appeared limited, and objective responses have been observed in a few patients. In malignant gliomas, intra-tumoral injections of CpG-ODN represent a practical approach. Indeed, human gliomas display a locally invasive pattern of growth and rarely metastasize, making local treatment clinically relevant.
The cellular immune response depends on the delivery of lymphocytes from the lymph node to the peripheral site of antigenic challenge. During their passage through the inflammatory microcirculaton, the migratory cells can become transiently immobilized or "trapped" in small caliber vessels. In this report, we used intravital microscopy and temporal area mapping to define the dynamic deformation of efferent lymph-derived mononuclear cells trapped in the systemic inflammatory microcirculation. Mononuclear cells obtained from the efferent lymph draining the oxazolone-stimulated microcirculation were labeled with fluorescent dye and reinjected into the feeding arterial circulation. Intravital video microscopy observed thousands of cells passing through the microcirculation; 35 cells were "trapped" in the oxazolone-stimulated microcirculation. Temporal area maps of the trapped cells demonstrated dramatic slowing and deformation. The cells were trapped in the microcirculation for a median of 8.90 sec (range 5-17 sec) prior to returning to the flow stream. During this period, the cells showed sustained movement associated with both antegrade locomotion (mean cell velocity = 7.92 microm/sec; range 1.16-14.23 microm/sec) and dynamic elongation (median cell length = 73.8 microm; range 58-144 microm). In contrast, efferent lymph-derived cells passing unimpeded through the microcirculation demonstrated rapid velocity (median velocity = 216 microm/sec) and spherical geometry (median diameter = 14.6 microm). Further, the membrane surface area of the "trapped" cells, calculated based on digital image morphometry and corrosion cast scanning electron microscopy, suggested that the fractional excess membrane of the cells in the efferent lymph was significantly greater than previous estimates of membrane excess. These data indicate that transient immobilization of efferent lymph-derived mononuclear cells in the systemic inflammatory microcirculation is rare. When "trapping" does occur, the shape changes and sustained cell movement facilitated by excess cell membrane may contribute to the return of the "trapped cells" into the flow stream.