Antitumoral immune responses

McKallip RJ, Nagarkatti M, Nagarkatti PS. Delta-9-tetrahydrocannabinol enhances breast cancer growth and metastasis by suppression of the antitumor immune response. J Immunol 2005 174 3281-9. 

K. Krenek, M. Kuldova, K. Hulfkova, I. Stibor, P. Lhotak, M. Dudic, J. Budka, H. Pelantova, K. Bezouska, A. Fiserova, and V. Kren, /V-Acetyl-D-glucosamine substituted calix[4]arenes as stimulators of NK cell-mediated antitumor immune response, Carbohydr. Res., 342 (2007) 1781-1792. 

To review, in an experimental mouse model, LPDI/E7 vaccination both prevents the establishment of metastatic E7-expressing tumors in naive mice through an induced E7-specific T-cell immune response and, in mice with previously established E7-expressing tumors, causes tumor regression with one subcutaneous injection of LPDI/E7 [Han SJ, et al. Subcutaneous antigen loading of dendritic cells by liposome-protamine-DNA (LPD) nanoparticles results in their activation and induction of specific antitumor immune response (impublished)]. A robust immune response follows administration of LPDI/ peptide particles, which can be used as either a preventative or therapeutic cancer vaccination strategy due to the ability of the particles to prevent and eliminate tumors, respectively, in mouse models. 

Whitmore MM, et al. Systemic administration of LPD prepared with CpG oligonucleotides inhibits the growth of established pulmonary metastases by stimulating innate and acquired antitumor immune responses. Cancer Immunol Immunother 2001 50 503. 

Cytokines have been under clinical investigation as adjuvants to vaccines, and IFNs and IL-2 have shown some positive effects in the response of human subjects to hepatitis vaccine. IL-12 and GM-CSF have also shown adjuvant effects with vaccines. GM-CSF is of particular interest because it promotes recruitment of professional antigen-presenting cells such as the dendritic cells required for priming naive antigen-specific T-lymphocyte responses. There are some claims that GM-CSF can itself stimulate an antitumor immune response, resulting in tumor regression in melanoma and prostate cancer. 

The phase I and phase II trials of therapeutic vaccines (Table 3.) show a weak toxicity of lipids A, furthermore they show a stimulation of the acquired antitumoral immune response. CTL responses correlate better than antibody responses to clinical outcomes, in agreement with current concepts of antitumor immunity. Phase m trials are now necessary to determine the effective protocol. 

Tan, J., Yang, N.S., Turner, J.G., Niu, G.L., Maassab, H.F., Sun, J. etal. (1999) Interleukin-12 cDNA skin transfection potentiates human papillomavirus E6 DNA vaccine-induced antitumor immune response. Cancer Gene Then, 6, 331-339. 

Many SCLC patients mount an antitumor immune response without signs of PNS [9, 167, 174]. Nevertheless, most SCLC patients do not have this immune response. Thus, the rarity of PNS cannot be attributed to infrequency of antigen expression. This discrepancy suggests that additional factors, perhaps related to tumor major histocompatibility complex (MHC) expression, contribute to the initiation of the PNS immune response. A study of Hu antigen and MHC class I expression in SCLC and neuroblastoma supports this theory. Seventeen of 20 tumors from Hu antibody positive patients expressed both proteins, but only 4 of 30 specimens from seronegative individuals expressed both proteins [171]. Altered expression and/or down-regulation of MHC molecules is a common immune-evasive strategy of tumor cells [175],... 

Another approach to induce a GVT effect in patients who relapse following HSCT is to administer a cytokine posttransplant with immunomodulatory activity, such as interleukin-2 (IL-2)." Some beneficial effects have been observed with the use of IL-2 with respect to effects on natural killer cells and other important antitumor immune responses. Toxicities have been tolerable in most patients but can be serious and life-threatening. Studies are necessary to define the role of these cytokines in prolonging relapse-free survival after HSCT. 

ABSTRACT In mammals, nitric oxide (NO) is a reactive free radical involved in diverse physiological functions. NO and its redox-related forms NO+ and NO react with di(oxygen) and its derivatives, with metalloproteins and thiol-containing proteins. NO-mediated nitrosation of proteins represents an important cellular regulatory mechanism. Biosynthesis of NO is catalysed by nitric oxide synthase (NOS). Three isoenzymes representing distinct gene products have been identified the inducible NOS isoform, the constitutive neuronal and endothelial isoforms. Inducible and constitutive NOSs have the same structural features, but their activities differ in their dependence to calcium and the rate of NO produced. The principal NO-mediated functions in mammals are endothelium-dependent relaxation, neurotransmission and immune response. The role of NO in the antitumor immune response comprises both regulatory and effector functions at the intra- or inter-cellular level. The first function includes inhibition of lymphocyte proliferation or participation in different transduction pathways. The second fiinction includes pro- or anti-tumoral effects and NO-mediated cell toxicity or cell resistance to apoptosis. 

Considering the impressive and diversified literature related to NO in animals, we have had to be selective in the present review. In the first part, we have attempted to give a general view of NO chemistry. Then, in a second part we described the biosynthesis of NO in mammals and detailed its role in the antitumor immune response. The first and second parts serve as background to the third part focalised on the recent advances on NO functions in plants. 

Therefore, NO is a mediator of antitumoral immune responses. If undoubtedly NO is one effector of macrophages mediated tumor cell toxicity in vitro, its role in NK and LAK mediated tumor cell toxicity is doubtfull. 

Therefore, the role of NO in the antitumor immune response, comprises both regulatory and effector functions at the intra- or intercellular level. The first functions includes inhibition of lymphocyte proliferation or participation in different transduction pathways. The second functions include pro- or anti-tumoral effects and NO mediated cell toxicity or cell resistance to apoptosis. 

Nishikawa H, Kato T, Tanida K, et al. (2003). CD4 CD25 T cells responding to serologically defined autoantigens suppress antitumor immune responses. Proc. Natl. Acad. Sci. U.S.A. 100(19) 10902-10906. 

Yamanaka R, Zullo SA, Ramsey J, Yajima N, Tsuchiya N, Tanaka R, Blaese M, Xanthopoulos KG. Marked enhancement of antitumor immune responses in mouse brain tumor models by genetically modified dendritic cells producing semliki forest virus-mediated interleukin-12. J Neurosurg 2002 97 611—618. 

Chen HW, Huang HI, Lee YP, Chen LL, Liu HK, Cheng ML, Tsai JP, Tao MH, Ting CC. Linkage of CD401 to a self-tumor antigen enhances the antitumor immune responses of dendritic cell-based treatment. Cancer Immunol Immunother 2002 51 341-348. 

Induction of antitumor immune responses by using tumor-specific antigens is a cherished goal in cancer therapeutics since it promises to be free of dose-limiting... 

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