Biomedical subjects

R Sussman

Publications and source records attributed to R Sussman.

5 recordsLinked to original sources

PubMed2025

HLA-E and NKG2A Mediate Resistance to BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Bacillus Calmette-Guérin (BCG) is the first-line therapy for high-grade non-muscle-invasive bladder cancer (NMIBC), yet many patients experience recurrence due to immune evasion. We identify HLA-E and NKG2A as mediators of adaptive resistance involving chronic activation of NK and T cells in BCG-unresponsive tumors. Prolonged IFN-γ exposure enhances HLA-E and PD-L1 expression on recurrent tumors, accompanied by the accumulation of NKG2A+ NK and CD8 T cells. HLA-Ehigh tumor cells preferentially cluster near CXCL12-rich stromal regions with dense effector cell presence, underscoring a spatially segregated tumor architecture. Although cytotoxic lymphocytes retain effector potential, their activity is restrained by HLA-E/NKG2A and PD-L1/PD-1 pathways located in their immediate neighborhood within the bladder tumor microenvironment. These data reveal a spatially organized immune escape program that limits anti-tumor immunity. Our findings support dually targeting NKG2A and PD-L1 checkpoint blockade as a rational, bladder-sparing strategy for patients with BCG-unresponsive NMIBC.

BCG-unresponsive↗

PubMed1978

Interaction of bacteriophage lambda repressor with nonoperator DNA containing single-strand gaps.

In direct binding assays, purified lambdaind+ repressor displayed high affinity for nonoperator DNA containing single-strand gaps. Its affinity for this same DNA but completely double-stranded, nicked, or denatured was considerably lower. In contrast, purified lambdaind- repressor had 1/10th the affinity for the gapped DNA, a level comparable to that of purified lac repressor. In the presence of limiting amounts of ind+ repressor, nonoperator DNA containing gaps could be shown to compete effectively with lambda DNA for binding of repressor. A previous model of lambda induction [Sussman, R. & Ben-Zeev, H. (1975) Proc. Natl. Acad. Sci. USA 72, 1973--1976], based on the assumption that this phenomenon involves the binding of repressor to lesions in the host DNA, is reevaluated in the light of the data reported here.

Binding Sites↗

PubMed1978

Correlation between UV dose requirement for lambda bacteriophage induction and lambda repressor concentration.

Escherichia coli K-12 wild type and a uvrA mutant derivative were used to construct isogenic strains bearing one, two, three, or more phage lambda cI genomes and containing increasing concentration of lambda repressor as measured by in vitro operator DNA-binding assays. The survival and phage induction in response to UV irradiation were determined. In both strains, dose-response relationships were obtained as a function of the cellular repressor concentration. The uvrA lysogens required one-tenth the UV fluence of the wild-type counterparts for induction. Lysogenic strains containing plasmids that overproduce the lambdaind+ repressor and the same lysogens with plasmids overproducing the lambdaind- repressor displayed the same survival curves as the nonlysogenic parental strain; however, only the former produced infectious centers (at a frequency of 2 x 10(-3) to 5 x 10(-4) in response to radiation.

Coliphages↗

PubMed1977

Effect of strain variation and growth phase of culture on dry weight and hexosamine content of cell wall layers of a marine pseudomonad.

Two variants of marine pseudomonad B-16 (ATCC 19855) differing in that one, variant 3, formed opaque colonies and the other, variant 7, formed translucent colonies were examined to determine if the variants differed in the amount and hexosamine content of their three outer cell wall layers. In both variants, the three outer layers of the cell wall, the loosely bound outer layer, the outer double-track layer, and the underlying (periplasmic space) layer contributed less to the dry weight of the cells when the cells were harvested in the stationary than in the logarithmic phase of growth. The hexosamine content of the layers of variant 3 increased dramatically as the cells went from the logarithmic to the stationary phase. The hexosamine content of the layers of variant 7 changed little by comparison. Thus cells of the variant which forms opaque colonies enrich the outer layers of their cell wall with hexosamine when grown to stationary phase.

Cell Wall↗

PubMed1975

Proposed mechanism of bacteriophage lambda induction: acquisition of binding sites for lambda repressor by DNA of the host.

Interference with the in vitro binding of lambda phage repressor to lambda operator DNA was observed when Escherichia coli DNA containing the following lesions was present in the reaction mixture: (a) DNA with single-strand breaks from pancreatic DNase (nicked DNA); (B) DNA isolated from thymine-straved cells; (c) DNA from ultraviolet-treated cells; (d) DNA of mitomycin-treated cells; and (e) DNA from a temperature-sensitive ligase mutant after 1 hr at 42 degrees. Normal E. coli DNA did not interfere. Binding of lambda cIing-minus repressor to operator DNA was not affected by E. coli DNA with lesions. DNAs from cells treated with increasing doses of mitomycin were proportionately more effective in competition for repressor, suggesting increasing binding sites per unit of DNA. A general model of virus induction is proposed, based on binding affinity of ultraviolet-sensitive repressors for single-strand breaks in the host DNA. The model is extended also to the presumptive repressor of cell division.

Binding Sites↗