Vol 14, No 4 (2018)
Review paper
Published online: 2019-02-12

open access

Page views 1772
Article views/downloads 663
Get Citation

Connect on Social Media

Connect on Social Media

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

Izabela Chmielewska1, Michał Szczyrek12, Kamila Wojas-Krawczyk1, Aleksandra Grzywna1, Janusz Milanowski1, Paweł Krawczyk1
Oncol Clin Pract 2018;14(4):226-231.

Abstract

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.

Article available in PDF format

View PDF Download PDF file

References

  1. Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018; 359(6382): 1350–1355.
  2. Yao S, Chen L. PD-1 as an immune modulatory receptor. Cancer J. 2014; 20(4): 262–264.
  3. Weber JS, Hodi FS, Wolchok JD, et al. Safety Profile of Nivolumab Monotherapy: A Pooled Analysis of Patients With Advanced Melanoma. J Clin Oncol. 2017; 35(7): 785–792.
  4. Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006; 124(4): 837–848.
  5. Malinowska M, Tokarz-Deptuła B, Deptuła W. Mikrobiom człowieka. Post. Mikrobiol. 2017; 56(1): 33–42.
  6. Gopalakrishnan V, Spencer CN, Nezi L, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018; 359(6371): 97–103.
  7. Matson V, Fessler J, Bao R, et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018; 359(6371): 104–108.
  8. Sivan A, Corrales L, Hubert N, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015; 350(6264): 1084–1089.
  9. Thompson J, Szabo A, Arce-Lara C, et al. Microbiome and immunotherapy: Antibiotic use is associated with inferior survival for lung cancer patients receiving PD-1 inhibitors. . 2017; 12(11).
  10. Routy B, Chatelier ELe, Derosa L, et al. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science. 2017; 359(6371): 91–97.
  11. Derosa L, Routy B, Enot D, et al. Impact of antibiotics on outcome in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors. Journal of Clinical Oncology. 2017; 35(6_suppl): 462–462.
  12. Kaderbhai C, Richard C, Fumet JD, et al. Antibiotic Use Does Not Appear to Influence Response to Nivolumab. Anticancer Res. 2017; 37(6): 3195–3200.
  13. Sears CL, Pardoll DM. The intestinal microbiome influences checkpoint blockade. Nat Med. 2018; 24(3): 254–255.
  14. Nallasamy P, Chava S, Verma SS, et al. PD-L1, inflammation, non-coding RNAs, and neuroblastoma: Immuno-oncology perspective. Semin Cancer Biol. 2017 [Epub ahead of print].