Tumor antigen-specific CD4+ T cells in cancer immunity: from antigen identification to tumor prognosis and development of therapeutic strategies.

CD4(+) T cells comprise a large fraction of tumor infiltrating lymphocytes and it is now established that they may exert an important role in tumor immune-surveillance. Several CD4(+) T cell subsets [i.e. T helper (Th)1, Th2, T regulatory (Treg), Th17, Th22 and follicular T helper (Tfh)] have been described and differentiation of each subset depends on both the antigen presenting cells responsible for its activation and the cytokine environment present at the site of priming. Tumor antigen-specific CD4(+) T cells with different functional activity have been found in the blood of cancer patients and different CD4(+) T cell subsets have been identified at the tumor site by the expression of specific transcription factors and the profile of secreted cytokines. Importantly, depending on the subset, CD4(+) T cells may exert antitumor versus pro-tumor functions. Here we review the studies that first identified the presence of tumor-specific CD4(+) T cells in cancer patients, the techniques used to identify the tumor antigens recognized, the role of the different CD4(+) T cell subsets in tumor immunity and in cancer prognosis and the development of therapeutic strategies aimed at activating efficient antitumor CD4(+) T cell effectors.

Isolation and characterization of a mucin-glycoprotein from rat submandibular glands.

A blood group A+ mucin-glycoprotein was purified from aqueous extracts of rat submandibular glands by sequential chromatography on columns of Sepharose CL-6B and Sephacryl S-300 in urea-containing buffers. Final purification was facilitated by reductive methylation which appeared to release contaminating (hydrophobic) peptides. Homogeneity of the purified mucin was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis at varying concentrations of acrylamide, lectin affinity chromatography, and Western blot analysis. In contrast to previously described preparations, the purified mucin contained only trace amounts of N-acetylglucosamine and aromatic amino acids. In addition, only low levels of basic amino acids were present.

Adsorption of human salivary mucins to hydroxyapatite.

The interactions between low (MG2) and high (MG1) molecular-weight human submandibular-sublingual mucin and hydroxyapatite (OHAp) were compared using a quantitative assay. Data obtained appeared to empirically fit the Langmuir adsorption isotherm. Apparent affinity constants derived from this isotherm indicated that MG1 had a greater affinity for OHAp than did MG2. Inhibition studies revealed that salivary glycolipids inhibited the interaction of MG1 and OHAp without influencing MG2 adsorption. In contrast, MG2 adsorption to OHAp was markedly inhibited by cysteine-containing salivary phosphoprotein fractions. Collectively, the data indicate MG1 and MG2 differ in their interaction with OHAp.

Isolation and characterization of tracheobronchial mucin from a laryngectomee.

A tracheobronchial mucin was isolated from the tracheobronchial secretion of a laryngectomee. It was purified by gel filtration on Sepharose CL-6B in Tris-urea buffer and rechromatography of excluded materials through the same gel matrix. It was homogeneous in 0.7% agarose-2% polyacrylamide electrophoresis under nonreducing conditions. Comparable analysis with 2-mercaptoethanol revealed at least 3 subunits. Based upon recoverable weight, the mucin was composed of 75% carbohydrate, 21% protein, and 3% sulfate. Oligosaccharides obtained by alkaline beta-elimination indicated O-glycosyl linkage to the peptide component. Marked heterogeneity of the carbohydrate side-chains was reflected in the preparation of 20 distinct oligosaccharides ranging in size from 4 to 17 residues.