Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2018

Open Access 01-12-2018 | Review

Gut microbiome modulates efficacy of immune checkpoint inhibitors

Authors: Ming Yi, Shengnan Yu, Shuang Qin, Qian Liu, Hanxiao Xu, Weiheng Zhao, Qian Chu, Kongming Wu

Published in: Journal of Hematology & Oncology | Issue 1/2018

Login to get access

Abstract

Immune checkpoint inhibitors (ICIs) therapy is a novel strategy for cancer treatments in recent years. However, it was observed that most patients treated with ICIs could not get benefit from the therapy, which led to the limitation of clinical application. Motivated by potent and durable efficacy of ICIs, oncologists endeavor to explore the mechanisms of resistance to ICIs and increase the drug sensitivity. It is known that heterogeneity of gut microbiome in populations may result in different outcomes of therapy. In xenograft model, bacteria in gut have been proved as a crucial factor regulating immunotherapy efficacy. And the similar phenomenon was obtained in patients. In this review, we summarized relevant advancements about gut microbiome and ICIs. Furthermore, we focused on modulatory function of gut microbiome in ICIs therapy and possible antitumor mechanism of specific commensals in ICIs treatment. We propose that gut microbiome is an important predictive factor, and manipulation of gut microbiome is feasible to elevate response rate in ICIs therapy.
Literature
1.
2.
Filyk HA, Osborne LC. The multibiome: the intestinal ecosystem’s influence on immune homeostasis, health, and disease. EBioMedicine. 2016;13:46–54.PubMedPubMedCentralCrossRef
3.
4.
5.
Tai N, Wong FS, Wen L. The role of gut microbiota in the development of type 1, type 2 diabetes mellitus and obesity. Rev Endocr Metab Disord. 2015;16:55–65.PubMedPubMedCentralCrossRef
6.
7.
8.
Tlaskalova-Hogenova H, Stepankova R, Hudcovic T, Tuckova L, Cukrowska B, Lodinova-Zadnikova R, et al. Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. Immunol Lett. 2004;93:97–108.PubMedCrossRef
9.
Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, Stonebraker AC, et al. Innate immunity and intestinal microbiota in the development of type 1 diabetes. Nature. 2008;455:1109–13.PubMedPubMedCentralCrossRef
10.
Lee Y, Awasthi A, Yosef N, Quintana FJ, Xiao S, Peters A, et al. Induction and molecular signature of pathogenic TH17 cells. Nat Immunol. 2012;13:991–9.PubMedPubMedCentralCrossRef
11.
Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359:97–103.PubMedCrossRef
12.
Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillere R, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359:91–7.PubMedCrossRef
13.
Haanen JB, Robert C. Immune checkpoint inhibitors. Prog Tumor Res. 2015;42:55–66.PubMed
14.
15.
Long J, Lin J, Wang A, Wu L, Zheng Y, Yang X, et al. PD-1/PD-L blockade in gastrointestinal cancers: lessons learned and the road toward precision immunotherapy. J Hematol Oncol. 2017;10:146.PubMedPubMedCentralCrossRef
16.
Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:23–34.PubMedPubMedCentralCrossRef
17.
Weber JS, D'Angelo SP, Minor D, Hodi FS, Gutzmer R, Neyns B, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2015;16:375–84.PubMedCrossRef
18.
Hodi FS, Chesney J, Pavlick AC, Robert C, Grossmann KF, McDermott DF, et al. Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 2016;17:1558–68.PubMedPubMedCentralCrossRef
19.
O'Donnell JS, Long GV, Scolyer RA, Teng MW, Smyth MJ. Resistance to PD1/PDL1 checkpoint inhibition. Cancer Treat Rev. 2017;52:71–81.PubMedCrossRef
20.
Ma W, Gilligan BM, Yuan J, Li T. Current status and perspectives in translational biomarker research for PD-1/PD-L1 immune checkpoint blockade therapy. J Hematol Oncol. 2016;9:47.PubMedPubMedCentralCrossRef
21.
22.
Bultman SJ. The microbiome and its potential as a cancer preventive intervention. Semin Oncol. 2016;43:97–106.PubMedCrossRef
23.
Karasov WH, Martinez del Rio C, Caviedes-Vidal E. Ecological physiology of diet and digestive systems. Annu Rev Physiol. 2011;73:69–93.PubMedCrossRef
24.
25.
Kamada N, Seo SU, Chen GY, Nunez G. Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol. 2013;13:321–35.PubMedCrossRef
26.
Carpenter MR, Rozovsky S, Boyd EF. Pathogenicity Island cross talk mediated by recombination directionality factors facilitates excision from the chromosome. J Bacteriol. 2015;198:766–76.PubMedCrossRef
27.
28.
Hirota K, Turner JE, Villa M, Duarte JH, Demengeot J, Steinmetz OM, et al. Plasticity of Th17 cells in Peyer’s patches is responsible for the induction of T cell-dependent IgA responses. Nat Immunol. 2013;14:372–9.PubMedPubMedCentralCrossRef
29.
Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science. 2011;331:337–41.PubMedCrossRef
30.
Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell. 2005;122:107–18.PubMedCrossRef
31.
Daillere R, Vetizou M, Waldschmitt N, Yamazaki T, Isnard C, Poirier-Colame V, et al. Enterococcus hirae and Barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects. Immunity. 2016;45:931–43.PubMedCrossRef
32.
Mao K, Baptista AP, Tamoutounour S, Zhuang L, Bouladoux N, Martins AJ, et al. Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolism. Nature. 2018;554:255–9.PubMedCrossRef
33.
34.
Quince C, Walker AW, Simpson JT, Loman NJ, Segata N. Shotgun metagenomics, from sampling to analysis. Nat Biotechnol. 2017;35:833–44.PubMedCrossRef
35.
Okazaki T, Chikuma S, Iwai Y, Fagarasan S, Honjo TA. Rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application. Nat Immunol. 2013;14:1212–8.PubMedCrossRef
36.
37.
Yamazaki T, Akiba H, Iwai H, Matsuda H, Aoki M, Tanno Y, et al. Expression of programmed death 1 ligands by murine T cells and APC. J Immunol. 2002;169:5538–45.PubMedCrossRef
38.
Botticelli A, Zizzari I, Mazzuca F, Ascierto PA, Putignani L, Marchetti L, et al. Cross-talk between microbiota and immune fitness to steer and control response to anti PD-1/PDL-1 treatment. Oncotarget. 2017;8:8890–9.PubMed
39.
40.
Azuma K, Ota K, Kawahara A, Hattori S, Iwama E, Harada T, et al. Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer. Ann Oncol. 2014;25:1935–40.PubMedCrossRef
41.
Parry RV, Chemnitz JM, Frauwirth KA, Lanfranco AR, Braunstein I, Kobayashi SV, et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol Cell Biol. 2005;25:9543–53.PubMedPubMedCentralCrossRef
42.
Patsoukis N, Brown J, Petkova V, Liu F, Li L, Boussiotis VA. Selective effects of PD-1 on Akt and Ras pathways regulate molecular components of the cell cycle and inhibit T cell proliferation. Sci Signal. 2012;5:ra46.PubMedPubMedCentralCrossRef
43.
Wang J, Yuan R, Song W, Sun J, Liu D, Li Z. PD-1, PD-L1 (B7-H1) and tumor-site immune modulation therapy: the historical perspective. J Hematol Oncol. 2017;10:34.PubMedPubMedCentralCrossRef
44.
Wilson RAM, Evans TRJ, Fraser AR, Nibbs RJB. Immune checkpoint inhibitors: new strategies to checkmate cancer. Clin Exp Immunol. 2018;191:133–48.PubMedCrossRef
45.
Rowshanravan B, Halliday N, Sansom DM. CTLA-4: a moving target in immunotherapy. Blood. 2018;131:58–67.PubMed
46.
Walker LS, Sansom DM. The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses. Nat Rev Immunol. 2011;11:852–63.PubMedCrossRef
47.
Soskic B, Qureshi OS, Hou T, Sansom DMA. Transendocytosis perspective on the CD28/CTLA-4 pathway. Adv Immunol. 2014;124:95–136.PubMedCrossRef
48.
49.
50.
Wang GX, Kurra V, Gainor JF, Sullivan RJ, Flaherty KT, Lee SI, et al. Immune checkpoint inhibitor cancer therapy: spectrum of imaging findings. Radiographics. 2017;37:2132–44.PubMedCrossRef
51.
52.
53.
54.
Ozaki Y, Shindoh J, Miura Y, Nakajima H, Oki R, Uchiyama M, et al. Serial pseudoprogression of metastatic malignant melanoma in a patient treated with nivolumab: a case report. BMC Cancer. 2017;17:778.PubMedPubMedCentralCrossRef
55.
Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372:2521–32.PubMedCrossRef
56.
Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002;3:991–8.PubMedCrossRef
57.
Koyama S, Akbay EA, Li YY, Herter-Sprie GS, Buczkowski KA, Richards WG, et al. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun. 2016;7:10501.PubMedPubMedCentralCrossRef
58.
Jin HT, Anderson AC, Tan WG, West EE, Ha SJ, Araki K, et al. Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection. Proc Natl Acad Sci U S A. 2010;107:14733–8.PubMedPubMedCentralCrossRef
59.
Zhou Q, Munger ME, Veenstra RG, Weigel BJ, Hirashima M, Munn DH, et al. Coexpression of Tim-3 and PD-1 identifies a CD8+ T-cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia. Blood. 2011;117:4501–10.PubMedPubMedCentralCrossRef
60.
Holmgaard RB, Zamarin D, Munn DH, Wolchok JD, Allison JP. Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4. J Exp Med. 2013;210:1389–402.PubMedPubMedCentralCrossRef
61.
Munn DH, Sharma MD, Hou D, Baban B, Lee JR, Antonia SJ, et al. Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes. J Clin Invest. 2004;114:280–90.PubMedPubMedCentralCrossRef
62.
Young A, Mittal D, Stagg J, Smyth MJ. Targeting cancer-derived adenosine: new therapeutic approaches. Cancer Discov. 2014;4:879–88.PubMedCrossRef
63.
Allard B, Turcotte M, Spring K, Pommey S, Royal I, Stagg J. Anti-CD73 therapy impairs tumor angiogenesis. Int J Cancer. 2014;134:1466–73.PubMedCrossRef
64.
Beavis PA, Divisekera U, Paget C, Chow MT, John LB, Devaud C, et al. Blockade of A2A receptors potently suppresses the metastasis of CD73+ tumors. Proc Natl Acad Sci U S A. 2013;110:14711–6.PubMedPubMedCentralCrossRef
65.
Terp MG, Olesen KA, Arnspang EC, Lund RR, Lagerholm BC, Ditzel HJ, et al. Anti-human CD73 monoclonal antibody inhibits metastasis formation in human breast cancer by inducing clustering and internalization of CD73 expressed on the surface of cancer cells. J Immunol. 2013;191:4165–73.PubMedCrossRef
66.
Wang L, Tang S, Wang Y, Xu S, Yu J, Zhi X, et al. Ecto-5′-nucleotidase (CD73) promotes tumor angiogenesis. Clin Exp Metastasis. 2013;30:671–80.PubMedCrossRef
67.
Maj T, Wang W, Crespo J, Zhang H, Wang W, Wei S, et al. Oxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumor. Nat Immunol. 2017;18:1332–41.PubMedPubMedCentralCrossRef
68.
Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, et al. Commensal bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350:1084–9.PubMedPubMedCentralCrossRef
69.
Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre ML, et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018;359:104–8.PubMedCrossRef
70.
Vetizou M, Pitt JM, Daillere R, Lepage P, Waldschmitt N, Flament C, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015;350:1079–84.PubMedPubMedCentralCrossRef
71.
Irrazabal T, Martin A. T regulatory cells gone bad: an oncogenic immune response against enterotoxigenic B. Fragilis infection leads to colon cancer. Cancer Discov. 2015;5:1021–3.PubMedCrossRef
72.
Chaput N, Lepage P, Coutzac C, Soularue E, Le Roux K, Monot C, et al. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. Ann Oncol. 2017;28:1368–79.PubMedCrossRef
73.
74.
Zitvogel L, Galluzzi L, Viaud S, Vetizou M, Daillere R, Merad M, et al. Cancer and the gut microbiota: an unexpected link. Sci Transl Med. 2015;7:271ps1.PubMedPubMedCentralCrossRef
75.
76.
77.
78.
Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillere R, Hannani D, et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science. 2013;342:971–6.PubMedPubMedCentralCrossRef
79.
Mima K, Nakagawa S, Sawayama H, Ishimoto T, Imai K, Iwatsuki M, et al. The microbiome and hepatobiliary-pancreatic cancers. Cancer Lett. 2017;402:9–15.PubMedCrossRef
80.
Roy S, Trinchieri G. Microbiota: a key orchestrator of cancer therapy. Nat Rev Cancer. 2017;17:271–85.PubMedCrossRef
81.
Alexander JL, Wilson ID, Teare J, Marchesi JR, Nicholson JK, Kinross JM. Gut microbiota modulation of chemotherapy efficacy and toxicity. Nat Rev Gastroenterol Hepatol. 2017;14:356–65.PubMedCrossRef
82.
Vetizou M, Daillere R, Zitvogel L. The role of intestinal microbiota in the response to anti-tumor therapies. Med Sci (Paris). 2016;32:974–82.CrossRef
83.
Pitt JM, Vetizou M, Waldschmitt N, Kroemer G, Chamaillard M, Boneca IG, et al. Fine-tuning cancer immunotherapy: optimizing the gut microbiome. Cancer Res. 2016;76:4602–7.PubMedCrossRef
84.
Honda K, Littman DR. The microbiota in adaptive immune homeostasis and disease. Nature. 2016;535:75–84.PubMedCrossRef
85.
Spranger S, Sivan A, Corrales L, Gajewski TF. Tumor and host factors controlling antitumor immunity and efficacy of cancer immunotherapy. Adv Immunol. 2016;130:75–93.PubMedPubMedCentralCrossRef
86.
West NR, Powrie F. Immunotherapy not working? Check Your Microbiota Cancer Cell. 2015;28:687–9.PubMed
87.
Hefazi M, Patnaik MM, Hogan WJ, Litzow MR, Pardi DS, Khanna S. Safety and efficacy of fecal microbiota transplant for recurrent clostridium difficile infection in patients with cancer treated with cytotoxic chemotherapy: a single-institution retrospective case series. Mayo Clin Proc. 2017;92:1617–24.PubMedCrossRef
88.
Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013;504:446–50.PubMedCrossRef
89.
Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermudez-Humaran LG, Gratadoux JJ, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A. 2008;105:16731–6.PubMedPubMedCentralCrossRef
90.
Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly YM, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341:569–73.PubMedCrossRef
91.
Dubin K, Callahan MK, Ren B, Khanin R, Viale A, Ling L, et al. Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis. Nat Commun. 2016;7:10391.PubMedPubMedCentralCrossRef
92.
Wei SC, Levine JH, Cogdill AP, Zhao Y, Anang NAS, Andrews MC, et al. Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade. Cell. 2017;170:1120–33.e17.PubMedCrossRef
93.
Jacquelot N, Enot DP, Flament C, Vimond N, Blattner C, Pitt JM, et al. Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma. J Clin Invest. 2016;126:921–37.PubMedPubMedCentralCrossRef
94.
Mullins IM, Slingluff CL, Lee JK, Garbee CF, Shu J, Anderson SG, et al. CXC chemokine receptor 3 expression by activated CD8+ T cells is associated with survival in melanoma patients with stage III disease. Cancer Res. 2004;64:7697–701.PubMedCrossRef
95.
Carbonnel F, Soularue E, Coutzac C, Chaput N, Mateus C, Lepage P, et al. Inflammatory bowel disease and cancer response due to anti-CTLA-4: is it in the flora? Semin Immunopathol. 2017;39:327–31.PubMedCrossRef
96.
Peters S, Kerr KM, Stahel R. PD-1 blockade in advanced NSCLC: a focus on pembrolizumab. Cancer Treat Rev. 2017;62:39–49.PubMedCrossRef
97.
Donohoe DR, Garge N, Zhang X, Sun W, O'Connell TM, Bunger MK, et al. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab. 2011;13:517–26.PubMedPubMedCentralCrossRef
98.
Blacher E, Levy M, Tatirovsky E, Elinav E. Microbiome-modulated metabolites at the Interface of host immunity. J Immunol. 2017;198:572–80.PubMedCrossRef
99.
100.
Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541:321–30.PubMedCrossRef
101.
102.
103.
Zitvogel L, Pitt JM, Daillere R, Smyth MJ, Kroemer G. Mouse models in oncoimmunology. Nat Rev Cancer. 2016;16:759–73.PubMedCrossRef
104.
Wheeler ML, Limon JJ, Bar AS, Leal CA, Gargus M, Tang J, et al. Immunological consequences of intestinal fungal dysbiosis. Cell Host Microbe. 2016;19:865–73.PubMedPubMedCentralCrossRef
105.
Kernbauer E, Ding Y, Cadwell K. An enteric virus can replace the beneficial function of commensal bacteria. Nature. 2014;516:94–8.PubMedPubMedCentral
106.
Young GR, Eksmond U, Salcedo R, Alexopoulou L, Stoye JP, Kassiotis G. Resurrection of endogenous retroviruses in antibody-deficient mice. Nature. 2012;491:774–8.PubMedPubMedCentral
107.
Zitvogel L, Daillere R, Roberti MP, Routy B, Kroemer G. Anticancer effects of the microbiome and its products. Nat Rev Microbiol. 2017;15:465–78.PubMedCrossRef
Metadata
Title
Gut microbiome modulates efficacy of immune checkpoint inhibitors
Authors
Ming Yi
Shengnan Yu
Shuang Qin
Qian Liu
Hanxiao Xu
Weiheng Zhao
Qian Chu
Kongming Wu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2018
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-018-0592-6

Other articles of this Issue 1/2018

Journal of Hematology & Oncology 1/2018 Go to the issue

Research

Long-term effects of ruxolitinib versus best available therapy on bone marrow fibrosis in patients with myelofibrosis

Research

MET alterations detected in blood-derived circulating tumor DNA correlate with bone metastases and poor prognosis

Research

Inhibition of thioredoxin activates mitophagy and overcomes adaptive bortezomib resistance in multiple myeloma

Letter to the Editor

Predictors of atrial fibrillation in ibrutinib-treated CLL patients: a prospective study

Letter to the Editor

Myeloma-derived macrophage inhibitory factor regulates bone marrow stromal cell-derived IL-6 via c-MYC

Review

The consensus on indications, conditioning regimen, and donor selection of allogeneic hematopoietic cell transplantation for hematological diseases in China—recommendations from the Chinese Society of Hematology
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits