Body mass index as a predictor of the efficacy of immune checkpoint inhibitors in patients with non-small cell lung cancer and other solid tumors
Abstract
Body mass index (BMI) has been increasingly recognized as a potential predictor of response to immune chec k point inhibitor (ICI) therapy across various malignancies. This study aimed to evaluate the association between BMI and clinical outcomes in patients with non-small cell lung cancer (NSCLC) and other solid tumors receiving ICIs. In this retrospective cohort study, 158 patients were included and analyzed. Clinicopathological characteristics such as BMI, Eastern Cooperative Oncology Group (ECOG) performance status, PD-L1 expression level, tumor histology, and the presence of distant metastases, including central nervous system (CNS) involvement, were comprehensively assessed. Survival outcomes, including progression-free survival (PFS) and overall survival (OS), were estimated using Kaplan–Meier survival curves, while independent prognostic factors were identified through multivariate Cox proportional hazards regression analysis . Patients with obesity (BMI > 30) demonstrated significantly improved survival outcomes compared with patients of normal weight, overweight, and underweight categories . Specifically, the median PFS was 11.2 months in obese patients versus 6.8 months in normal-weight individuals, while the median OS reached 22.2 months compared with 12.2 months, respectively. These findings remained statistically significant after adjustment for other clinicopathological variables. Multivariate analysis confirmed BMI, ECOG performance status, PD-L1 expre s sion, tumor histology, and CNS metastases as independent predictors of both PFS and OS. The observed association between higher BMI and improved response to ICIs may be explained by immunometabolic mechanisms, including chronic low-grade inflammation, altered cytokine profiles, and leptin-mediated modulation of the PD-1/PD-L1 axis, potentially enhancing antitumor immune responses. These results suggest that BMI represents a simple, accessible, and cost-effective biomarker that can be readily incorporated into routine clinical practice. Therefore, patient selection for immunotherapy should consider BMI in conjunction with established prognostic factors such as ECOG performance status, PD-L1 expression, tumor histology, and metastatic burden, particularly CNS involvement. Overall, these findings support the prognostic and predictive value of BMI and highlight its potential role in optimizing individualized treatment strategies in patients receiving immune checkpoint inhibitors.References
Bu, L. L., Yu, G. T., Wu, L., Mao, L., Deng, W. W., Liu, J. F., Kulkarni, A. B., Zhang, W. F., Zhang, L., & Sun, Z. J. (2017). STAT3 induces immunosuppression by upregulating PD-1/PD-L1 in HNSCC. Journal of Dental Research, 96(9), 1027–1034.
Daste, A., Larroquette, M., Gibson, N., Lasserre, M., & Domblides, C. (2024). Immunotherapy for head and neck squamous cell carcinoma: Current status and perspectives. Immunotherapy, 16(3), 187–197.
Davern, M., Bracken-Clarke, D., Donlon, N. E., Sheppard, A. D., Connell, F. O., Heeran, A. B., Majcher, K., Conroy, M. J., Mylod, E., Butler, C., Donohoe, C., O’Donnell, D., Lowery, M., Bhardwaj, A., Ravi, N., Melo, A. A., O’Sullivan, J., Reynolds, J. V., & Lysaght, J. (2023). Visceral adipose tissue secretome from early and late-stage oesophageal cancer patients differentially affects effector and regulatory T cells. Journal of Cancer Research and Clinical Oncology, 149(9), 6583–6599.
De Giorgi, U., Procopio, G., Giannarelli, D., Sabbatini, R., Bearz, A., Buti, S., Basso, U., Mitterer, M., Ortega, C., Bidoli, P., Ferraù, F., Crinò, L., Frassoldati, A., Marchetti, P., Mini, E., Scoppola, A., Verusio, C., Fornarini, G., Cartenì, G., Caserta, C., & Sternberg, C. N. (2019). Association of systemic inflammation index and body mass index with survival in patients with renal cell cancer treated with nivolumab. Clinical Cancer Research, 25(13), 3839–3846.
Deng, G., Zhu, D., Du, Z., Xue, Y., Song, H., & Li, Y. (2024). Body composition change indices combined with Prognostic Nutritional Index predicts the clinical outcomes of patients with gastric cancer treated with immune checkpoint inhibitor. Cancer Medicine, 13(6), e7110.
Du, W., Sirbu, C., Lucas, B. D., Jr., Jubelirer, S. J., Khalid, A., & Mei, L. (2021). A retrospective study of brain metastases from solid malignancies: The effect of immune checkpoint inhibitors. Frontiers in Oncology, 11, 667847.
Ged, Y., Sanchez, A., Patil, S., Knezevic, A., Stein, E., Petruzella, S., Weiss, K., Duzgol, C., Chaim, J., Akin, O., Mourtzakis, M., Paris, M. T., Scott, J., Kuo, F., Kotecha, R., Hakimi, A. A., Lee, C. H., Motzer, R. J., Voss, M. H., & Furberg, H. (2022). Associations between pretreatment body composition features and clinical outcomes among patients with metastatic clear cell renal cell carcinoma treated with immune checkpoint blockade. Clinical Cancer Research, 28(23), 5180–5189.
Ged, Y., Sanchez, A., Patil, S., Knezevic, A., Stein, E., Petruzella, S., Weiss, K., Duzgol, C., Chaim, J., Akin, O., Mourtzakis, M., Paris, M. T., Scott, J., Kuo, F., Kotecha, R., Hakimi, A. A., Lee, C. H., Motzer, R. J., Voss, M. H., & Furberg, H. (2022). Associations between pretreatment body composition features and clinical outcomes among patients with metastatic clear cell renal cell carcinoma treated with immune checkpoint blockade. Clinical Cancer Research, 28(23), 5180–5189.
Holder, A. M., Dedeilia, A., Sierra-Davidson, K., Cohen, S., Liu, D., Parikh, A., & Boland, G. M. (2024). Defining clinically useful biomarkers of immune checkpoint inhibitors in solid tumours. Nature Reviews Cancer, 24(7), 498–512.
Huang, S. Y., Su, P. J., Lin, C. T., Kuo, M. C., Chen, Y. H., Wu, C. C., Luo, H. L., Chen, C. H., Chou, C. C., Huang, C. C., Kuo, C. W., & Su, Y. L. (2024). The impact of body mass index on survival endpoints among patients with metastatic urothelial carcinoma undergoing treatment with immune checkpoint inhibitors: A real-world multicenter analysis. Cancer Medicine, 13(2), e7008.
Ichihara, E., Harada, D., Inoue, K., Sato, K., Hosokawa, S., Kishino, D., Watanabe, K., Ochi, N., Oda, N., Hara, N., Hotta, K., Maeda, Y., & Kiura, K. (2020). The impact of body mass index on the efficacy of anti-PD-1/PD-L1 antibodies in patients with non-small cell lung cancer. Lung Cancer, 139, 140–145.
Jin, X., Wu, M., Dong, S., Liu, H., & Ma, H. (2024). Artificially sweetened beverages consumption and risk of obesity-related cancers: A wide-angled Mendelian randomization study. Frontiers in Nutrition, 11, 1347724.
Kraakman, M. J., Murphy, A. J., Jandeleit-Dahm, K., & Kammoun, H. L. (2014). Macrophage polarization in obesity and type 2 diabetes: Weighing down our understanding of macrophage function? Frontiers in Immunology, 5, 470.
Li, Y., Liang, X., Li, H., & Chen, X. (2023). Efficacy and safety of immune checkpoint inhibitors for advanced non-small cell lung cancer with or without PD-L1 selection: A systematic review and network meta-analysis. Chinese Medical Journal, 136(18), 2156–2165.
Mojibi, Y., Seif, F., Mojibi, N., Aghamajidi, A., Mohsenzadegan, M., & Torang, H. A. (2022). Efficacy of immunotherapy in obese patients with cancer. Immunopharmacology and Immunotoxicology, 44(4), 471–483.
Moskalenko, Y. V. (2025f). IFNγ-associated gene signature as a potential prognostic biomarker of survival and immunotherapy response in lung adenocarcinoma. Journal of V. N. Karazin National University, Series Medicine, 33(4), 510–522.
Moskalenko, Y. V., Bohdanov, A. M., & Budko, V. V. (2025c). Smoking as a predictor of immune checkpoint inhibitor efficacy in metastatic non-small cell lung cancer patients. East Ukrainian Medical Journal, 13(4), 1168–1176.
Moskalenko, Y., & Moskalenko, R. (2025e). Prognostic significance of immune phenotypes in patients with metastatic non-small cell lung cancer. Journal of V. N. Karazin National University, Series Medicine, 33(5), 689–702.
Moskalenko, Y., Kovchun, V., Bohdanov, A., & Budko, V. (2026h). Subcutaneous adipose tissue radiodensity as a prognostic marker in metastatic non-small cell lung cancer treated with immune checkpoint inhibitors. Contemporary Oncology/Współczesna Onkologia, 30(1), 1–9.
Moskalenko, Y., Kovchun, V., Bohdanov, A., Budko, V., & Yazykov, O. (2025g). Visceral adipose tissue radiodensity as a potential biomarker of immunotherapy efficacy in metastatic non-small cell lung cancer patients. Galician Medical Journal, 32(3), e-GMJ2025-A21.
Moskalenko, Y., Kovchun, V., Vynnychenko, I., & Moskalenko, R. (2025d). Association of skeletal muscle radiodensity and skeletal muscle index with immunotherapy response in metastatic non-small cell lung cancer. Muscles, 4(4), 51.
Moskalenko, Y., Kravets, O., & Kovchun, V. (2025b).Clinical outcomes of concurrent use of corticosteroids and immune checkpoint inhibitors in oncology. Regulatory Mechanisms in Biosystems, 16(2), e25062.
Moskalenko, Y., Yazykov, O., Vasylieva, O., Smiian, K., Ivakhniuk, T., Budko, H., & Moskalenko, R. (2025a). The impact of age on the effectiveness of immune checkpoint inhibitors therapy in patients with metastatic non-small-cell lung cancer. Geriatrics, 10(4), 85.
Quintanilha, J. C. F., Storandt, M. H., Graf, R. P., Li, G., Keller, R., Lin, D. I., Ross, J. S., Huang, R. S. P., Schrock, A. B., Oxnard, G. R., Chakrabarti, S., & Mahipal, A. (2023). Tumor mutational burden in real-world patients with pancreatic cancer: Genomic alterations and predictive value for immune checkpoint inhibitor effectiveness. JCO Precision Oncology, 7, e2300092.
Roccuzzo, G., Moirano, G., Fava, P., Maule, M., Ribero, S., & Quaglino, P. (2023). Obesity and immune-checkpoint inhibitors in advanced melanoma: A meta-analysis of survival outcomes from clinical studies. Seminars in Cancer Biology, 91, 27–34.
Rosellini, M., Massafra, R., Santoni, M., & Massari, F. (2023). The impact of ECOG performance status on efficacy of immunotherapy and immune-based combinations in cancer patients: The MOUSEION-06 study. Clinical and Experimental Medicine, 23(8), 5039–5049.
Vallejo, J., Singh, H., Larkins, E., Drezner, N., Ricciuti, B., Mishra-Kalyani, P., Tang, S., Beaver, J. A., & Awad, M. M. (2024). Impact of increasing PD-L1 levels on outcomes to PD-1/PD-L1 inhibition in patients with NSCLC: A pooled analysis of 11 prospective clinical trials. The Oncologist, 29(5), 422–430.
Vithayathil, M., D'Alessio, A., Fulgenzi, C. A. M., Nishida, N., Schönlein, M., von Felden, J., Schulze, K., Wege, H., Saeed, A., Wietharn, B., Hildebrand, H., Wu, L., Ang, C., Marron, T. U., Weinmann, A., Galle, P. R., Bettinger, D., Bengsch, B., Vogel, A., Balcar, L., Scheiner, B., Lee, P. C., Huang, Y. H., Amara, S., Muzaffar, M., Naqash, A. R., Cammarota, A., Zanuso, V., Pressiani, T., Pinter, M., Cortellini, A., Kudo, M., Rimassa, L., Pinato, D. J., & Sharma, R. (2023). Impact of body mass index in patients receiving atezolizumab plus bevacizumab for hepatocellular carcinoma. Hepatology International, 17(4), 904–914.
Wang, Z., Aguilar, E. G., Luna, J. I., Dunai, C., Khuat, L. T., Le, C. T., Mirsoian, A., Minnar, C. M., Stoffel, K. M., Sturgill, I. R., Grossenbacher, S. K., Withers, S. S., Rebhun, R. B., Hartigan-O'Connor, D. J., Méndez-Lagares, G., Tarantal, A. F., Isseroff, R. R., Griffith, T. S., Schalper, K. A., Merleev, A., Saha, A., Maverakis, E., Kelly, K., Aljumaily, R., Ibrahimi, S., Mukherjee, S., Machiorlatti, M., Vesely, S. K., Longo, D. L., Blazar, B. R., Canter, R. J., Murphy, W. J., & Monjazeb, A. M. (2019). Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade. Nature Medicine, 25(1), 141–151.
Woodall, M. J., Neumann, S., Campbell, K., Pattison, S. T., & Young, S. L. (2020). The effects of obesity on anti-cancer immunity and cancer immunotherapy. Cancers, 12(5), 1230.
Xiao, L. S., Li, R. N., Cui, H., Hong, C., Huang, C. Y., Li, Q. M., Hu, C. Y., Dong, Z. Y., Zhu, H. B., & Liu, L. (2022). Use of computed tomography-derived body composition to determine the prognosis of patients with primary liver cancer treated with immune checkpoint inhibitors: A retrospective cohort study. BMC Cancer, 22(1), 737.
Yang, F., Markovic, S. N., Molina, J. R., Halfdanarson, T. R., Pagliaro, L. C., Chintakuntlawar, A. V., Li, R., Wei, J., Wang, L., Liu, B., Nowakowski, G. S., Wang, M. L., & Wang, Y. (2020). Association of sex, age, and Eastern Cooperative Oncology Group performance status with survival benefit of cancer immunotherapy in randomized clinical trials: A systematic review and meta-analysis. JAMA Network Open, 3(8), e2012534.
Yoneda, T., Sone, T., Koba, H., Shibata, K., Suzuki, J., Tani, M., Nishitsuji, M., Nishi, K., Kobayashi, T., Shirasaki, H., Araya, T., Kita, T., Kase, K., Yamamura, K., Terada, N., Nishikawa, S., Tambo, Y., Kimura, H., & Kasahara, K. (2022). Long-term survival of patients with non-small cell lung cancer treated with immune checkpoint inhibitor monotherapy in real-world settings. Clinical Lung Cancer, 23(6), 467–476.
Zhang, T., Li, S., Chang, J., Qin, Y., & Li, C. (2023). Impact of BMI on the survival outcomes of non-small cell lung cancer patients treated with immune checkpoint inhibitors: A meta-analysis. BMC Cancer, 23(1), 1023.
Zheng, J., Shao, M., Yang, W., Ren, J., Chen, X., & Yang, H. (2022). Benefits of combination therapy with immune checkpoint inhibitors and predictive role of tumour mutation burden in hepatocellular carcinoma: A systematic review and meta-analysis. International Immunopharmacology, 112, 109244.
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