Improvement in immune dysfunction after FOLFOX chemotherapy for Stage III colon cancer is associated with improved minimal residual disease prognostic subtype and outcome

Abstract

Aim: Minimal residual disease (MRD) is the net result of the biological properties of disseminated tumour cells and the effect of the immune system and treatment to eliminate them. The aim of this work is to report the changes in MRD status and immune function (lymphocyte count) after FOLFOX chemotherapy, and the outcome in Stage III colon cancer patients.Method: This study is a prospective, single-centre observational study. Lymphocyte counts were determined prior to and 1, 2 and 3 months after the completion of chemotherapy. Circulating tumour cells (CTCs) and bone marrow micrometastases were determined using immunocytochemistry with anticarcinoembryonic antigen prior to and 1 month after chemotherapy. MRD was classified as negative (Group I), micrometastasis positive only (Group II) and CTC positive (Group III). Changes in lymphocyte counts and MRD subtype following chemotherapy and relapse-free progression were analysed.Results: Of the total of 185 patients, 83 (44.9%) relapsed. The risk of relapse significantly increased from Groups I to III (p < 0.001) and with decreasing lymphocyte count (p < 0.01). The lymphocyte count significantly decreased from Groups I to III (p < 0.001).Multivariance Cox regression analysis showed hazard ratios of 3.58 (Group II), 17.43 (Group III) and 0.39 (lymphocyte count) in predicting relapse. Following chemotherapy, improved lymphocyte count was associated with improved MRD subtype (p < 0.0001).Neither baseline lymphocyte count nor MRD subtype predicted response to chemotherapy. Five-year relapse-free survival for combined lymphocyte-MRD subtypes was 95%, 57% and 5% for Groups I to III, respectively (p < 0.001). Conclusion:Following chemotherapy, improvements in immune function were associated with improved MRD subtype and a better relapse-free survival.

Is Laparoscopic Complete Mesocolic Excision and Central Vascular Ligation Really Necessary for All Patients With Right-Sided Colon Cancer?

“…The greater the lymphocyte infiltration in the tumor and the more tumor antigen expression relating to microsatellite instability, the greater the immune response and the immunological defense against cancer. A strong immune response may be manifested by an increase in the number of harvested lymph nodes after surgery [ 73 ]. Since various questions about the therapeutic effect of harvested lymph nodes remain, contemporary surgeons are still performing radical D3 dissection, and the oncological necessity of CME with CVL remains valid to date.…”

Comparison of NOD-like and Toll-like receptors gene expression levels in blood monocytes of colon cancer patients

“…In addition to their role in the homeostasis of immune responses, these cells are also important in tissue repair and fighting cancers such as colon cancer (15). On the surface of monocytes, there are various pattern recognition receptors, especially TLRs, which, by recognizing the presence of microbes and their products in their signaling pathway, initiate primary immune responses against infection and tissue damage (16). NLRs, as another group of pattern recognition receptors in monocytes, by starting several inflammatory messenger pathways, lead to the initiation of the inflammasome complex and the secretion of mature forms of IL-18 and IL-1β, which create chronic conditions in the microenvironment of cancer cells (17).…”