Spontaneous regression͞complete resistance (SR͞CR) mice resist very high doses of cancer cells that are lethal to WT mice even at low doses. In this study, we show that this resistance is mediated by rapid infiltration of leukocytes, mostly of innate immunity, in both primary and repeated challenges. Formation of rosettes with infiltrating natural killer cells, neutrophils, and macrophages was required for the subsequent destruction of cancer cells through rapid cytolysis. Highly purified natural killer cells, macrophages, and neutrophils from the SR͞CR mice independently killed cancer cells in vitro. The independent killing activity by each subset of effector cells is consistent with the observation that the resistance was abolished by depleting total infiltrating leukocytes but not by depleting only one or two subsets of leukocytes. The resistance was completely transferable to WT recipient mice through SR͞CR splenocytes, bone marrow cells, or enriched peritoneal macrophages, either for prevention against subsequent cancer challenges or eradication of established malignancy at distant sites. cellular cancer immunity ͉ adoptive transfer ͉ cancer therapy ͉ macrophages ͉ leukocyte depletion

Human minor histocompatibility Ags (mHag) present significant barriers to successful bone marrow transplantation. However, the structure of human mHag and the basis for antigenic disparities are still largely unknown. Here we report the identification of the gene encoding the human mHag HA-2 as a previously unknown member of the class I myosin family, which we have designated MYO1G. The gene is located on the short arm of chromosome 7. Expression of this gene is limited to cells of hemopoietic origin, in keeping with the previously defined tissue expression of the HA-2 Ag. RT-PCR amplification of MYO1G from different individuals led to the identification of two genetic variants, designated MYO1GV and MYO1GM. The former encodes the peptide sequence previously shown to be the HA-2 epitope (YIGEVLVSV), whereas the latter shows a single amino acid change in this peptide (YIGEVLVSM). This change has only a modest effect on peptide binding to the class I MHC-restricted element HLA-A*0201, and a minimal impact on recognition by T cells when added exogenously to target cells. Nonetheless, as detected using either T cells or mass spectrometry, this amino acid change results in a failure of the latter peptide to be presented at the surface of cells that express MYO1GM endogenously. These studies have thus identified a new mHag-encoding gene, and thereby provide additional information about both the genetic origins of human mHag as well as the underlying basis of an Ag-positive vs Ag-negative state.

Formation of mature spermatozoa involves a series of dramatic molecular and morphological changes in the male germ cell lineage. These changes result from the temporally regulated transcription and translation of several testis-specific gene products. Here, we describe a novel, testis-specific protein designated SPAN-X for sperm protein associated with the nucleus on the X chromosome. SPAN-X sequences showed no significant similarity with known cDNA or peptide sequences. The SPAN-X peptide sequences contained three overlapping consensus nuclear localization signals, a high percentage (33%-37%) of charged amino acid residues, and a relatively acidic isoelectric point (pI; 4.88-6.05). Northern analysis of mRNA from multiple human tissues identified a SPAN-X transcript exclusively in the testis. In situ hybridization of human testes sections showed SPAN-X mRNA expression in haploid, round, and elongating spermatids. The SPANX gene was mapped to chromosome Xq27. 1 by fluorescence in situ hybridization and by Southern blot analysis of human/mouse somatic cell hybrids. On Western blots of human sperm proteins, antirecombinant SPAN-X antibodies reacted with broad bands migrating between 15-20 kDa. Immunofluorescent labeling of human spermatozoa demonstrated SPAN-X localization to nuclear craters and cytoplasmic droplets. Expression of SPAN-X, an X-linked gene product, exclusively in haploid spermatids leads to interesting questions regarding the transcription of sex-linked genes during spermiogenesis.

Purpose: Chromosome 6q14-21is commonly deleted in prostate cancers, occurring in f22% of all tumors and f40% of metastatic tumors. However, candidate prostate tumor suppressor genes in this region have not been identified, in part due to the large and broad nature of the deleted region implicated in previous studies. Experimental Design: We first used high-resolution Affymetrix single nucleotide polymorphism arrays to examine DNA from malignant and matched nonmalignant cells from 55 prostate cancer patients. We identified a small consensus region on 6q14-21 and evaluated the deletion status within the region among additional 40 tumors and normal pairs using quantitative PCR and fluorescence in situ hybridization.We finally tested the association between the deletion and Gleason score using the Fisher's exact test. Results: Tumors with small, interstitial deletions at 6q14-21defined an 817-kb consensus region that is affected in 20 of 21tumors. The MAP3K7 gene is one of five genes located in this region. In total, MAP3K7 was deleted in 32% of 95 tumors. Importantly, deletion of MAP3K7 was highly associated with higher-grade disease, occurring in 61% of tumors with Gleason score z8 compared with only 22% of tumors with Gleason score V7. The difference was highly significant (P = 0.001). Conclusion: Our study provides strong evidence for the first time that a small deletion at 6q15, including the MAP3K7 gene and four other genes, is associated with high-grade prostate cancers. Although the deletion may be a marker for high-grade prostate cancer, additional studies are needed to understand its molecular mechanisms.Many if not most prostate cancers do not pose a major health threat to their hosts. The molecular factors responsible for variations in the aggressiveness of prostate cancers are poorly defined. Deletion of DNA sequences from chromosome 6q14-21 is one of the most common deletion events in the genome of prostate tumors (reviewed in ref. 1). In a recent study that estimated the frequency of DNA copy number alterations in the prostate cancer genome based on all published comparative genomic hybridization studies of prostate cancers, about one quarter of the 891 prostate cancers had a deletion at 6q14-21 (2). More importantly, the deletion seemed to be more common in metastatic/ advanced tumors (40%) than in localized/primary tumors (19%). Despite this overwhelming evidence for frequent 6q deletions, specific prostate tumor suppressor genes have not been identified in this region. One of the major obstacles is the size of the deleted region implicated in previous studies, due at least in part to limited resolution of the detection methods. In our combined analysis of all published comparative genomic hybridization studies, the deleted region at 6q spans f30 Mb (2). The large number of genes (>170) located within the broad deletion interval poses a significant challenge to effective searches for tumor suppressor genes in the region. Therefore, efforts are needed to define a smaller candidate region. Hi...

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