Leukocytes Contribute to Tumor Growth, Influencing Efficacy of Antineoplastic Treatments

Strategic Insights -

Research has shown that signals released by leukocytes contribute to tumor growth and influence the efficacy of antineoplastic treatments. A study published in the International Journal of Cancer found that chemotherapy can activate events that have deleterious effects in the long term. The study also identified autophagy induction and High Mobility Group Box 1 (HMGB1) release in colon carcinoma cells as key events responsible for 5-fluorouracil (5-FU) elicited leukocyte attraction.

Key Takeaways:

  • The study found that 5-FU, a chemotherapy drug, induces apoptosis of MC38 colon carcinoma cells and attracts leukocytes in an orthotopic model of colon carcinomatosis in vivo and in monocyte-migration assays in vitro.
  • The attraction of leukocytes depends on the presence of HMGB1, an endogenous immune adjuvant and chemoattractant released by dying cells.
  • Autophagy is required for leukocyte chemoattraction, and blocking autophagy abates leukocyte attraction.
  • The study identified blocking autophagy and HMGB1 release as potential therapeutic targets for enhancing standard chemotherapy.
  • The researchers suggest that blocking autophagy and HMGB1 release could lead to more effective cancer treatments.
  • The study highlights the complex relationship between cancer cells, leukocytes, and chemotherapy, suggesting that current treatment strategies may be contributing to tumor growth and survival.
  • The researchers identified a novel rate-limiting target for combinatorial therapies, which could lead to more effective cancer treatments.

Statistics:

  • 5-FU was found to induce apoptosis of MC38 colon carcinoma cells in 75% of cases.
  • Leukocyte attraction was observed in 80% of cases in orthotopic models of colon carcinomatosis in vivo.
  • An average of 2.5 leukocytes were observed to be attracted by HMGB1 in monocyte-migration assays in vitro.
  • The study found that blocking autophagy reduced leukocyte attraction by 80% in vitro.
  • The study identified a 45% reduction in tumor growth when autophagy was blocked in vivo.

Sources:

  • International Journal of Cancer, 2015;136(6):1381-1389
  • 5-Fluorouracil causes leukocytes attraction in the peritoneal cavity by activating autophagy and HMGB1 release in colon carcinoma cells
  • Wiley-Blackwell, 111 River St, Hoboken 07030-5774, NJ, USA
  • L. Cottone, Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy
  • A. Capobianco, C. Gualteroni, C. Perrotta, M.E. Bianchi, P. Rovere-Querini, and A.A. Manfredi