Modulation of CD(4)(+) and CD(8)(+) tumor infiltrating lymphocytes by a fraction isolated from shark cartilage: shark cartilage modulates anti-tumor immunity

Int Immunopharmacol. 2003 Jul;3(7):921-6. doi: 10.1016/S1567-5769(02)00255-2.


Shark cartilage has proven to have some inhibitory effects on angiogenesis, metastasis, cell adhesion and proteolysis. In this study, we wanted to study some of the effects of shark cartilage on tumor immune response. Firstly, by means of chromatographic methods and delayed type hypersensitivity (DTH) test, we optimized a procedure for isolation and purification of a shark cartilage protein fraction with most immunostimulatory effects. Then, we examined its effect on the infiltration of CD(4)(+) and CD(8)(+) lymphocytes into a murine tumor model. Our fraction was composed of two major proteins with molecular weights (MWs) of about 14 and 15 kDa. This fraction highly increases DTH response against sRBC in mice. Furthermore, intraperitoneal injection of this fraction to tumor-bearing mice could increase T-cell infiltration into the tumor. Also, there was a significant increase in the CD(4)/CD(8) ratio in tumor infiltrating lymphocytes, but no such changes were found in the peripheral blood lymphocytes. According to these results, we suppose that this fraction is a good candidate for further studies in cancer therapy. Also, we concluded that this fraction, with previously proven anti-angiogenic effects, can augment cellular immune response and T-cell infiltration into the tumor and thus, there may be a direct relationship between angiogenesis inhibition and T-cell infiltration.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / immunology
  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology*
  • Adjuvants, Immunologic / therapeutic use
  • Administration, Oral
  • Animals
  • CD4-CD8 Ratio*
  • Cartilage / chemistry*
  • Disease Models, Animal
  • Electrophoresis, Polyacrylamide Gel
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mammary Neoplasms, Experimental / immunology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Weight
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Peptides / therapeutic use
  • Sharks*


  • Adjuvants, Immunologic
  • Peptides