It is well established that neoplastic tissues often express early differentiation antigens that are found in embryonic tissues. Recent studies by us and others provide evidence that certain types of tumors also express antigens that cross-react immunologically with antigens (possibly differentiation antigens) expressed by spermatozoa. We will perform additional studies to determine which types of tumors bear such cross-reacting antigens and whether tumor immunity is altered in individuals with antisperm immunity. In the first series of experiments, we will use cytotoxicity, agglutination, immunofluorescence, and radioimmunoassay techniques to screen sera from cancer patients and tumor-bearing mice for antibodies that react with spermatozoa or other testicular antigens. We will further characterize the cross-reactivity of antispermatozoal antibody from tumor-bearing or sperm-immune humans and mice by antigen absorption studies and with a blot technique in which antigens are reacted with antisera after slab gel electrophoresis. In a second series of experiments, we will use transplantable tumors, chemical carcinogens, and spontaneous tumor models to study tumorigenesis in mice with high titers of antisperm antibodies as a result of vasectomy or hyperimmunization with syngeneic sperm antigens. We will focus on the development of those types of tumors that were cross-reactive with sperm antigens in the serological tests. In the third phase of this study, we will use in vivo cell transfer (Winn assay) and in vitro cytotoxicity tests to further investigate cellular and humoral immunological mechanisms affecting tumor growth in sperm-immune individuals. We have recently reported an increased incidence of spontaneous tumors after vasectomy in mice and are currently investigating this effect. We are characterizing cross-reacting antigens on testicular germ cells and cancer cells and studying the immunosuppressive effects of sperm and seminal plasma. (AG)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA042738-02
Application #
3184278
Study Section
Reproductive Biology Study Section (REB)
Project Start
1985-08-01
Project End
1988-02-28
Budget Start
1986-03-01
Budget End
1987-02-28
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
Anderson, D J (1990) Cell-mediated immunity and inflammatory processes in male infertility. Arch Immunol Ther Exp (Warsz) 38:79-86
Berkowitz, R S; Faris, H M; Hill, J A et al. (1990) Localization of leukocytes and cytokines in chorionic villi of normal placentas and complete hydatidiform moles. Gynecol Oncol 37:396-400
Hill, J A; Welch, W R; Faris, H M et al. (1990) Induction of class II major histocompatibility complex antigen expression in human granulosa cells by interferon gamma: a potential mechanism contributing to autoimmune ovarian failure. Am J Obstet Gynecol 162:534-40
Wolff, H; Politch, J A; Martinez, A et al. (1990) Leukocytospermia is associated with poor semen quality. Fertil Steril 53:528-36
Hill, J A; Cohen, J; Anderson, D J (1989) The effects of lymphokines and monokines on human sperm fertilizing ability in the zona-free hamster egg penetration test. Am J Obstet Gynecol 160:1154-9
Anderson, D J; Michaelson, J S; Johnson, P M (1989) Trophoblast/leukocyte-common antigen is expressed by human testicular germ cells and appears on the surface of acrosome-reacted sperm. Biol Reprod 41:285-93
Hill, J A; Anderson, D J (1989) Lymphocyte activity in the presence of peritoneal fluid from fertile women and infertile women with and without endometriosis. Am J Obstet Gynecol 161:861-4
Band, V; Hoffer, A P; Band, H et al. (1989) Antiproliferative effect of gossypol and its optical isomers on human reproductive cancer cell lines. Gynecol Oncol 32:273-7
Anderson, D J; Hill, J A (1988) Cell-mediated immunity in infertility. Am J Reprod Immunol Microbiol 17:22-30
Hill, J A; Faris, H M; Schiff, I et al. (1988) Characterization of leukocyte subpopulations in the peritoneal fluid of women with endometriosis. Fertil Steril 50:216-22

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