The impact of intestinal microflora on the effectiveness of immunotherapy with antibodies against immune checkpoints — case report and literature review

Inhibitors of immune checkpoints (anti-PD-1 or anti-PD-L1 monoclonal antibodies) are effective in non-small cell lung cancer treatment, significantly extending the overall survival of some patients. However, there are no predictive factors, which could allow precise qualification of cancer patients to immunotherapy. The best evaluated in this regard is the expression of PD-L1 molecule on tumour cells, the occurrence of which is associated with higher response rate and prolonged time to progression in patients undergoing immunotherapy. Some recent reports indicate that the composition of the patient’s intestinal microflora, the presence of inflammation, and antibiotic therapy used before or during immunotherapy may affect the effectiveness of anti-PD-1 or anti-PD-L1 antibodies. Disturbance of the body’s natural balance, e.g. due to the use of antibiotics, may reduce the effectiveness of immunotherapy. This may be due to a lack of stimulation of the immune system by antigens from bacteria found naturally in the gut. On the other hand, supplementing the microflora with the necessary ingredients can improve the effectiveness of immunotherapy. The future goal is to develop so-called “immunotherapeutic probiotics”, the use of which could enhance the effect of cancer immunotherapy.

[1]  Jedd D. Wolchok,et al.  Cancer immunotherapy using checkpoint blockade , 2018, Science.

[2]  D. Pardoll,et al.  The intestinal microbiome influences checkpoint blockade , 2018, Nature Medicine.

[3]  Laurence Zitvogel,et al.  Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors , 2018, Science.

[4]  E. Le Chatelier,et al.  Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients , 2018, Science.

[5]  Riyue Bao,et al.  The commensal microbiome is associated with anti–PD-1 efficacy in metastatic melanoma patients , 2018, Science.

[6]  S. Batra,et al.  PD-L1, inflammation, non-coding RNAs, and neuroblastoma: Immuno-oncology perspective. , 2017, Seminars in cancer biology.

[7]  A. Szabo,et al.  P1.07-008 Microbiome & Immunotherapy: Antibiotic Use Is Associated with Inferior Survival for Lung Cancer Patients Receiving PD-1 Inhibitors , 2017 .

[8]  R. Boidot,et al.  Antibiotic Use Does Not Appear to Influence Response to Nivolumab. , 2017, Anticancer research.

[9]  L. Zitvogel,et al.  Impact of antibiotics on outcome in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors. , 2017 .

[10]  D. Schadendorf,et al.  Safety Profile of Nivolumab Monotherapy: A Pooled Analysis of Patients With Advanced Melanoma. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  Jason B. Williams,et al.  Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy , 2015, Science.

[12]  Lieping Chen,et al.  PD-1 as an immune modulatory receptor. , 2014, Cancer journal.

[13]  R. Ley,et al.  Ecological and Evolutionary Forces Shaping Microbial Diversity in the Human Intestine , 2006, Cell.