Abdolkarim Sheikhi; Abdollah Jafarzadeh; Parviz Kokhaei; Mohammad Hojjat-Farsangi
Volume 13, Issue 3 , September 2016, , Pages 148-166
Abstract
Cancer immunotherapy (passive or active) involves treatments which promote the ability of the immune system to fight tumor cells. Several types of immunotherapeutic agents, such as monoclonal antibodies, immune checkpoint inhibitors, non-specific immunomodulatory agents, and cancer vaccines are currently ...
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Cancer immunotherapy (passive or active) involves treatments which promote the ability of the immune system to fight tumor cells. Several types of immunotherapeutic agents, such as monoclonal antibodies, immune checkpoint inhibitors, non-specific immunomodulatory agents, and cancer vaccines are currently under intensive investigation in preclinical and clinical trials. Cancer vaccines induce permanent activation of the immune system and may be considered the most promising method for cancer treatment, especially in combination with other agents of passive immunotherapy. Among various approaches to cancer vaccines, whole tumor cell vaccines have been attracting attention for several years. Despite their low to moderate clinical effects, these vaccines have numerous advantages. Their ability to generate immune responses against tumor-associated antigens reduces the possibility for tumor cells to escape and facilitates the development of “off-the-shelf” allogeneic tumor vaccines. Understanding the reciprocal interactions between tumor cells and leukocytes is a key to harness the full potential of whole cell vaccination. Cytokines are considered as potent immunomodulatory molecules which behave as adjuvants in whole tumor cell vaccines. Improved mechanistic understanding of key cytokines in tumor immunity will serve as a resource for rational design of whole cell cancer vaccines. Although there are several reports about the use of different immunostimulatory cytokines as adjuvants, interleukin (IL)-12 appears to have superior effects compared to other cytokines. This review describes the effects of IL-12 compared to other immunomodulatory cytokines, such as IL-2 and IL-15, and highlights its application in whole cell tumor vaccination.
Abdolkarim Sheikhi; Hossein B. Ganji; Razieh Sheikhi
Volume 4, Issue 2 , June 2007, , Pages 79-84
Abstract
Background: Uterine natural killer (uNK) cells are the most abundant leukocytes in pre-implantation endometrium and early pregnancy deciduas in humans and rodents. They are associated with structural changes in maternal spiral arteries but regulation of their re-cruitment and activation is incompletely ...
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Background: Uterine natural killer (uNK) cells are the most abundant leukocytes in pre-implantation endometrium and early pregnancy deciduas in humans and rodents. They are associated with structural changes in maternal spiral arteries but regulation of their re-cruitment and activation is incompletely understood. The major subpopulation of uNK cells in humans expresses CD56, the neural cell adhesion molecule (NCAM)-1 while their counterpart in mouse expresses asialoGM1, a brain ganglioside. Sympathetic nerves ex-press NCAM-1 which mediates homotypic binding. Sympathetic fibers innervate the me-sometrial vasculature but their relationship to the myometrial and decidual uNK cell re-cruitment is unknown. Objective: The present study aims to explore positional relation-ship between natural killer cells and distribution of nerves in decidualized mouse uterus. Methods: Immunohistochemistry and mRNA expression for the enzyme tyrosine hy-droxylase were used to map sympathetic nerve fibre distribution within C57BL/6 implan-tation sites and to address a relationship with uNK cells. Results: Tyrosine hydroxylase positive neurons were identified in the mesometrium closely associated with uterine arter-ies. Staining became gradually vanished as the nerves crossed the myometrium and en-tered the decidualized uterus. No neuronal stain was associated with the spiral arteries. Periodic Acid Schiff’s reactive uNK cells were absent from the mesentery, but abundant in decidua basalis where they are associated with non-innervated vessels. Conclusion: Data suggest that the recruitment of uNK progenitor cells to the uterus is unlikely to be dependent on signaling by the sympathetic nervous system