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
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Checkpoint Inhibitors | Research

Non–small cell lung cancer and immune checkpoint inhibitor therapy: does non-alcoholic fatty liver disease have an effect?

Authors: Yi Li, Bingxin Gong, Yusheng Guo, Weiwei Liu, Chao Chen, Shanshan Jiang, Feng Pan, Jiyu Song, Lian Yang, Guofeng Zhou

Published in: BMC Cancer | Issue 1/2024

Login to get access

Abstract

Background

Immunotherapy based on the application of immune checkpoint inhibitors (ICIs) is one of the standard treatments for advanced non-small cell lung cancer (NSCLC). Non-alcoholic fatty liver Disease (NAFLD) has demonstrated predictive value for response to immunotherapy in non-lung cancer types. Our study investigated the effect of NAFLD on the efficacy of real-life use of ICIs for patients with stage III / IV NSCLC.

Methods

The clinical and imaging data of patients with stage III / IV NSCLC who were first admitted to Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from March 2020 to July 2022 were retrospectively collected to ensure that they underwent at least one CT scan before treatment. A total of 479 patients were divided into the NAFLD group (Liver/Spleen density ratio ≤ 1) and the non-NAFLD group (Liver/Spleen density ratio > 1) by measuring the baseline liver and spleen CT value. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) of the patients were obtained.

Results

A total of 118 patients with NAFLD and 361 patients without NAFLD were included in the study. Patients with NAFLD tended to have higher BMI and higher total bilirubin compared to patients without NAFLD. The median duration of follow-up in the study was 22 m (IQR, 17–29 m). Both of 2 groups had a higher DCR (94% vs. 92%, p = 0.199) and ORR (38.1% vs. 44.9%, p = 0.452) respectively. There was no difference in efficacy between the two groups. In univariate analysis, NAFLD had no significant effect on PFS (p = 0.785) and OS (p = 0.851). Surprisingly, the presence of hypertension was observed to be associated with a higher OS (HR 1.471 95%CI 1.018–2.127, p = 0.040). Besides, based on multivariate analysis, lactic dehydrogenase was associated with PFS (HR 1.001 95%CI 1.000,1.002, p = 0.037) and OS (HR 1.002, 95%CI 1.001–1.003, p < 0.001).

Conclusions

Among patients with NSCLC, NAFLD did not result in changes in survival or disease progression after immune checkpoint inhibitor therapy.
Appendix
Available only for authorised users
Literature
1.
Howlader N, Forjaz G, Mooradian MJ, Meza R, Kong CY, Cronin KA, et al. The Effect of advances in lung-cancer treatment on population mortality. N Engl J Med. 2020;383(7):640–9.CrossRefPubMedPubMedCentral
2.
3.
Doroshow DB, Sanmamed MF, Hastings K, Politi K, Rimm DL, Chen L, et al. Immunotherapy in non-small cell lung cancer: facts and hopes. Clin Cancer Res. 2019;25(15):4592–602.CrossRefPubMedPubMedCentral
4.
Lahiri A, Maji A, Potdar PD, Singh N, Parikh P, Bisht B, et al. Lung cancer immunotherapy: progress, pitfalls, and promises. Mol Cancer. 2023;22(1):40.CrossRefPubMedPubMedCentral
5.
Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018;15(1):11–20.CrossRefPubMed
6.
Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73–84.CrossRefPubMed
7.
Brown ZJ, Fu Q, Ma C, Kruhlak M, Zhang H, Luo J, et al. Carnitine palmitoyltransferase gene upregulation by linoleic acid induces CD4(+) T cell apoptosis promoting HCC development. Cell Death Dis. 2018;9(6):620.CrossRefPubMedPubMedCentral
8.
Agosti P, Sabbà C, Mazzocca A. Emerging metabolic risk factors in hepatocellular carcinoma and their influence on the liver microenvironment. Biochim Biophys Acta Mol Basis Dis. 2018;1864(2):607–17.CrossRefPubMed
9.
Tilg H, Adolph TE, Dudek M, Knolle P. Non-alcoholic fatty liver disease: the interplay between metabolism, microbes and immunity. Nat Metab. 2021;3(12):1596–607.CrossRefPubMed
10.
Pfister D, Nunez NG, Pinyol R, Govaere O, Pinter M, Szydlowska M, et al. NASH limits anti-tumour surveillance in immunotherapy-treated HCC. Nature. 2021;592(7854):450–6.CrossRefPubMedPubMedCentral
11.
Ettinger DS, Wood DE, Aisner DL, Akerley W, Bauman JR, Bharat A, et al. Non-small cell lung cancer, version 3.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2022;20(5):497–530.CrossRefPubMed
12.
Group of Fatty Liver and Alcoholic Liver Disease, Chinese Society of Hepatology, Chinese Medical Doctor Association, Fatty Liver Disease Expert Committee, Chinese Medical Doctor Association. Guidelines of prevention and treatment for nonalcoholic fatty liver disease: a 2018 update. Zhonghua Gan Zang Bing Za Zhi. 2018;26(3):195–203.
13.
Park YS, Park SH, Lee SS, Kim DY, Shin YM, Lee W, et al. Biopsy-proven nonsteatotic liver in adults: estimation of reference range for difference in attenuation between the liver and the spleen at nonenhanced CT. Radiology. 2011;258(3):760–6.CrossRefPubMed
14.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.CrossRefPubMed
15.
Cheng TY, Cramb SM, Baade PD, Youlden DR, Nwogu C, Reid ME. The international epidemiology of lung cancer: latest trends, disparities, and tumor characteristics. J Thorac Oncol. 2016;11(10):1653–71.CrossRefPubMedPubMedCentral
16.
Rosato PC, Wijeyesinghe S, Stolley JM, Nelson CE, Davis RL, Manlove LS, et al. Virus-specific memory T cells populate tumors and can be repurposed for tumor immunotherapy. Nat Commun. 2019;10(1):567.CrossRefPubMedPubMedCentral
17.
Arrieta O, Barrón F, Ramírez-Tirado LA, Zatarain-Barrón ZL, Cardona AF, Díaz-García D, et al. Efficacy and Safety of pembrolizumab plus docetaxel vs docetaxel alone in patients with previously treated advanced non-small cell lung cancer: the PROLUNG phase 2 randomized clinical trial. JAMA Oncol. 2020;6(6):856–64.CrossRefPubMed
18.
Zeng MD, Fan JG, Lu LG, Li YM, Chen CW, Wang BY, et al. Guidelines for the diagnosis and treatment of nonalcoholic fatty liver diseases. J Dig Dis. 2008;9(2):108–12.CrossRefPubMed
19.
Bydder GM, Chapman RW, Harry D, Bassan L, Sherlock S, Kreel L. Computed tomography attenuation values in fatty liver. J Comput Tomogr. 1981;5(1):33–5.CrossRefPubMed
20.
Öcal O, Ingrisch M, Ümütlü MR, Peynircioglu B, Loewe C, van Delden O, et al. Prognostic value of baseline imaging and clinical features in patients with advanced hepatocellular carcinoma. Br J Cancer. 2022;126(2):211–8.CrossRefPubMed
21.
Utzschneider KM, Kahn SE, Polidori DC. Hepatic insulin extraction in NAFLD is related to insulin resistance rather than liver fat content. J Clin Endocrinol Metab. 2019;104(5):1855–65.CrossRefPubMed
22.
Peiseler M, Schwabe R, Hampe J, Kubes P, Heikenwälder M, Tacke F. Immune mechanisms linking metabolic injury to inflammation and fibrosis in fatty liver disease - novel insights into cellular communication circuits. J Hepatol. 2022;77(4):1136–60.CrossRefPubMed
23.
Heinrich B, Brown ZJ, Diggs LP, Vormehr M, Ma C, Subramanyam V, et al. Steatohepatitis impairs T-cell-directed immunotherapies against liver tumors in mice. Gastroenterology. 2021;160(1):331-45.e6.CrossRefPubMed
24.
Pinto E, Meneghel P, Farinati F, Russo FP, Pelizzaro F, Gambato M. Efficacy of immunotherapy in hepatocellular carcinoma: Does liver disease etiology have a role? Dig Liver Dis. 2024;56(4):579–88.CrossRefPubMed
25.
Meyer T, Galani S, Lopes A, Vogel A. Aetiology of liver disease and response to immune checkpoint inhibitors: An updated meta-analysis confirms benefit in those with non-viral liver disease. J Hepatol. 2023;79(2):e73–6.CrossRefPubMed
26.
Zhou J, Zhou F, Chu X, Zhao J, Wu Y, Zhao W, et al. Non-alcoholic fatty liver disease is associated with immune checkpoint inhibitor-based treatment response in patients with non-small cell lung cancer with liver metastases. Transl Lung Cancer Res. 2020;9(2):316–24.CrossRefPubMedPubMedCentral
27.
Dudek M, Pfister D, Donakonda S, Filpe P, Schneider A, Laschinger M, et al. Auto-aggressive CXCR6(+) CD8 T cells cause liver immune pathology in NASH. Nature. 2021;592(7854):444–9.CrossRefPubMed
28.
Kwo PY, Cohen SM, Lim JK. ACG Clinical Guideline: Evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017;112(1):18–35.CrossRefPubMed
29.
Jin HR, Wang J, Wang ZJ, Xi MJ, Xia BH, Deng K, et al. Lipid metabolic reprogramming in tumor microenvironment: from mechanisms to therapeutics. J Hematol Oncol. 2023;16(1):103.CrossRefPubMedPubMedCentral
30.
Kichenadasse G, Miners JO, Mangoni AA, Rowland A, Hopkins AM, Sorich MJ. Association between body mass index and overall survival with immune checkpoint inhibitor therapy for advanced non-small cell lung cancer. JAMA Oncol. 2020;6(4):512–8.CrossRefPubMed
31.
Indini A, Rijavec E, Ghidini M, Tomasello G, Cattaneo M, Barbin F, et al. Impact of BMI on Survival outcomes of immunotherapy in solid tumors: A Systematic Review. Int J Mol Sci. 2021;22(5):2628.CrossRefPubMedPubMedCentral
32.
Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol. 2008;9(7):629–35.CrossRefPubMed
33.
Miao K, Zhang X, Wang H, Si X, Ni J, Zhong W, et al. Real-world data of different immune checkpoint inhibitors for non-small cell lung cancer in China. Front Oncol. 2022;12:859938.CrossRefPubMedPubMedCentral
34.
Zhao TV, Li Y, Liu X, Xia S, Shi P, Li L, et al. ATP release drives heightened immune responses associated with hypertension. Sci Immunol. 2019;4(36):eaau6426.CrossRefPubMedPubMedCentral
35.
Zhu J, Naulaerts S, Boudhan L, Martin M, Gatto L, Van den Eynde BJ. Tumour immune rejection triggered by activation of alpha2-adrenergic receptors. Nature. 2023;618(7965):607–15.CrossRefPubMed
36.
Mezquita L, Auclin E, Ferrara R, Charrier M, Remon J, Planchard D, et al. Association of the Lung immune prognostic index with immune checkpoint inhibitor outcomes in patients with advanced non-small cell lung cancer. JAMA Oncol. 2018;4(3):351–7.CrossRefPubMedPubMedCentral
37.
Nogami A, Yoneda M, Iwaki M, Kobayashi T, Honda Y, Ogawa Y, et al. Non-invasive imaging biomarkers for liver steatosis in non-alcoholic fatty liver disease: present and future. Clin Mol Hepatol. 2023;29(Suppl):S123–35.CrossRefPubMed
Metadata
Title
Non–small cell lung cancer and immune checkpoint inhibitor therapy: does non-alcoholic fatty liver disease have an effect?
Authors
Yi Li
Bingxin Gong
Yusheng Guo
Weiwei Liu
Chao Chen
Shanshan Jiang
Feng Pan
Jiyu Song
Lian Yang
Guofeng Zhou
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-024-12295-6

Other articles of this Issue 1/2024

BMC Cancer 1/2024 Go to the issue

Research

Central nervous system metastases in breast cancer patients with germline BRCA pathogenic variants compared to non-carriers: a matched-pair analysis

Research

Real-world advantage and challenge of post-autologous stem cell transplantation MRD negativity in high-risk patients with double-hit multiple myeloma

Research

Role of beta-(1→3)(1→6)-D-glucan derived from yeast on natural killer (NK) cells and breast cancer cell lines in 2D and 3D cultures

Research

Astragaloside IV-PESV inhibits prostate cancer tumor growth by restoring gut microbiota and microbial metabolic homeostasis via the AGE-RAGE pathway

Research

Prognostic value and immunological role of PD-L1 gene in pan-cancer

Research

First-in-human study of GFH018, a small molecule inhibitor of transforming growth factor-β receptor I inhibitor, in patients with advanced solid tumors
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