Changes in the plasma levels of cytokines/chemokines for predicting the response to chemoradiation therapy in rectal cancer patients

Abstract

In the present study, we aimed to characterize the predictive value of cytokines/chemokines in rectal cancer (RC) patients receiving chemoradiation therapy (CRT). Blood samples were obtained pre- and post-CRT from 35 patients with advanced RC, who received neoadjuvant CRT followed by surgery, and the correlation between plasma levels of cytokines/chemokines and the response to CRT was analyzed. The pre-CRT levels of soluble CD40-ligand (sCD40L) and the post-CRT levels of chemokine ligand-5 (CCL-5) were significantly associated with the depth of tumor invasion and with venous invasion. In addition, a significant decrease in sCD40L and CCL-5, as well as in platelet counts, was associated with a favorable response to CRT. A significant correlation between pre-CRT platelet counts and sCD40L was observed in patients with a favorable response. By contrast, higher post-CRT interleukin (IL)-6 was associated with a poor response. Platelets, immune system and cancer cells, cross-linked through various cytokines/chemokines, appear to play an important role in the response to CRT, and by understanding their roles, new approaches for the improvement of the therapy might be proposed.

Soluble levels of sCD40L and s4‐1BB are associated with a poor prognosis in elderly patients with colorectal cancer

“…The proven association between lymphocyte and neutrophil relationship with CRC prognosis confirms the relationship between immunity and cancer; and it has been the object of interest of researchers to allow the modulation of this response for the purpose of control and even cure for neoplasms . The involvement of CD40 and CD40L in neoplastic disease is still controversial, as some studies on CD40L have shown improved antineoplastic immune response, while other studies have suggested that activation of CD40 by its ligand (CD40L) results in increased tumor growth and progression . The present study identified a reduction in CD40L‐expressing platelet levels as well as in platelet aggregates in 60 patients with CRC.…”

“…The present study identified a reduction in CD40L‐expressing platelet levels as well as in platelet aggregates in 60 patients with CRC. The reduction of CD40L expression leads to reduced antineoplastic immune response and inhibition of neoplastic cell apoptosis . The inflammatory mediators released during the antitumor immune response are of great current interest because they are possible predictive biomarkers of treatment response.…”

“…In addition, CD40L is expressed on the platelet surface and induces extrinsic coagulation cascade, activates dendritic cells and B and T lymphocytes. Such ability suggests that platelet‐derived CD40L communicates between innate and adaptive immunity . Activated platelets can release soluble CD40L (sCD40L) and account for approximately 95% of circulating sCD40L.…”

“…Such ability suggests that platelet-derived CD40L communicates between innate and adaptive immunity. [12][13][14][15][16][17] Activated platelets can release soluble CD40L (sCD40L) and account for approximately 95% of circulating sCD40L. CD40L is an essential cytokine that leads to the activation of a broad spectrum of immune cells.…”

Predictive and Prognostic Molecular Biomarkers for Response to Neoadjuvant Chemoradiation in Rectal Cancer

“…Tada et al examined concentration of IL-2, IL-4, IL-6, IL-10, interferon-gamma (IFN-γ), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), C-C motif chemokine ligand-5 (CCL-5), TNF-related apoptosis-inducing ligand (TRAIL) and soluble CD40-ligand, using a bead-based multiplex immunoassay in the plasma samples collected from 35 rectal cancer patients before and after nCRT. While none of cytokine levels before nCRT were significantly associated with response to nCRT, levels of IL-6 and TNF-α after nCRT were significantly higher in non-responders compared to responders, and also significant decrease of soluble CD40-ligand and CCL-5 after nCRT was observed in responders [125]. …”