Natural killer cells activity in a metastatic colorectal cancer patient with complete and long lasting response to therapy

Here we report a case of a 70-year-old man who received adjuvant chemotherapy with fluorouracile, folinic acid and oxaliplatin after a left hemicolectomy for a stage Ⅲb adenocarcinoma in May 2009. During followup he de-veloped abdominal lymphnodes metastases evidenced by positron emission tomography-computed tomography(PET-CT) scan and increase of carcinoembryonic antigen(CEA) level. Chemotherapy with capecitabine, oxaliplatin and bevacizumab was started in April 2012. Restaging showed a complete response and normalization of CEA. The patient received maintenance therapy with bevacizumab which was stopped in December 2013 for patient choice. In October 2014, a new increase in CEA was documented and PET-CT scan showed lung metastases. Analysis of RAS status revealed the absence of mutations, then the patient started a second-line chemotherapy with fluorouracile, folinic acid, irinotecan(folfiri) and panitumumab achieving, in January 2015, a complete response and normalization of CEA. Thereafter, folfiri was discontinued for toxicity; furthermore, upon the third occurrence of a grade 3 dermatologic toxicity, panitumumab was continued from June 2015 at 60% of the original dose and it was administered every three weeks. Until presentation of this case, the patient maintains a complete response, has no symptoms of disease and CEA is normal. Interestingly, this patient presented a high proportion of circulating natural killer(NK) cells(35.1%) with high cytotoxic activity against tumor cells. Study on the role of NK in patients with advanced colorectal cancer are ongoing.

Predictive immune biomarkers: an unattainable chimera?

Immune checkpoint blockade(ICB)with antibodies interfering with cytotoxic T lymphocyte antigen 4(CTLA-4)and the programmed cell death 1(PD-1)protein tremendously revolutionized therapy for advanced cancer.Nevertheless,the activity of such agents(ipilimumab and nivolumab)is limited to a 10–45%response rate in the context of unselected populations with advanced solid tumors.Several common cancer types have demonstrated a very low frequency of response(breast,prostate and colon cancers),and heterogeneous responses have been observed between distinct tumors within the same patient.Challenges to broad clinical applicability include identifying patients most likely to benefit from checkpoint inhibitors and overcoming resistance to ICB.The immune response is a dynamic and constantly evolving process due primarily to patient-dependent factors,including genetic and tumor microenvironment(TME)features,and secondarily to treatment interventions.