Cited by 137Cancer Immunotherapy and BiomarkersLung Cancer Treatments and MutationsFerroptosis and cancer prognosis

The DOI matches its Crossref record; 139 of the 142 references it cites were found in a registry or an index.

Combination therapy with PD-1/PD-L1 blockade in non-small cell lung cancer: strategies and mechanisms

Huang, Mu-Yang, Jiang, Xiao-Ming, Wang, Bing-Lin, Sun, Yang, Lu, Jin-Jian·2021·Pharmacology & Therapeutics

DOI 10.1016/j.pharmthera.2020.107694

Open this paper in CoChat — free account

Abstract

Programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade has been approved as the standard-of-care for the treatment of non-small cell lung cancer (NSCLC). Yet, the population of patients who benefit from the treatment remains modest, some of whom would get relapsed and progressed eventually. Combination therapy has emerged as an effective way to broaden beneficiaries from PD-1/PD-L1 immunotherapy and overcome or delay the resistance. In this review, we discuss the PD-1/PD-L1 blockade in combination with conventional chemotherapy, targeted therapy or immunotherapy. Meanwhile, we illustrate their underlying mechanisms in regulating the process of the cancer-immunity cycle, providing the rationale for the PD-1/PD-L1 blockade-based combination therapy. The challenges of combination regimens are also addressed.

Integrity signals

Registry

Crossref · 10.1016/j.pharmthera.2020.107694

Cites

139 of 139 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21492 · Cited by 84,109
Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer
Reck, M., Rodríguez-Abreu, D., Robinson, A. G., Hui, R., Csőszi, T., Fülöp, A., Gottfried, M., Peled, N., Tafreshi, A., Cuffe, S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1606774 · Cited by 10,089
Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer
Brahmer, J., Reckamp, K. L., Baas, P., Crinò, L., Eberhardt, W. E. E., Poddubskaya, E., Antonia, S., Pluzanski, A., Vokes, E. E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504627 · Cited by 8,447
Microenvironmental regulation of tumor progression and metastasis
Quail, D. F., & Joyce, J. A. (2013) · Nature Medicine · doi:10.1038/nm.3394 · Cited by 7,994
Oncology meets immunology: the cancer-immunity cycle.
Chen, D. S., & Mellman, I. (2013) · Immunity · doi:10.1016/j.immuni.2013.07.012 · Cited by 6,929
Cancer immunotherapy using checkpoint blockade
Ribas, A., & Wolchok, J. D. (2018) · Science · doi:10.1126/science.aar4060 · Cited by 6,791
Pembrolizumab plus chemotherapy in metastatic non–small-cell lung cancer
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., Domine, M., Clingan, P., Hochmair, M. J., Powell, S. F., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1801005 · Cited by 6,607
Pembrolizumab for the Treatment of Non–Small-Cell Lung Cancer
Garon, E. B., Rizvi, N. A., Hui, R., Leighl, N., Balmanoukian, A. S., Eder, J. P., Patnaik, A., Aggarwal, C., Gubens, M., Horn, L., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1501824 · Cited by 6,198
Understanding the tumor immune microenvironment (TIME) for effective therapy
Binnewies, M., Roberts, E. W., Kersten, K., Chan, V., Fearon, D. F., Merad, M., Coussens, L. M., Gabrilovich, D. I., Ostrand-Rosenberg, S., Hedrick, C. C., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0014-x · Cited by 6,145
TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells
Mariathasan, S., Turley, S. J., Nickles, D., Castiglioni, A., Yuen, K., Wang, Y., Kadel III, E. E., Koeppen, H., Astarita, J. L., Cubas, R., et al. (2018) · Nature · doi:10.1038/nature25501 · Cited by 5,400

Show all 142 references

Research works printed but not linked: 1

Massarelli, 2016, Clinical safety and efficacy assessment of the CD137 agonist urelumab alone and in combination with nivolumab in patients with hematologic and solid tumor malignancies, Journal for Immunotherapy of Cancer, 4, O7

Sorted by citations

Items 101–137 of 137

Cordyceps sinensis enhances the efficacy of anti-PD-1 immunotherapy in Lewis lung adenocarcinoma
Liu, Y., Gao, Y., Suonanlamao, Ma, Y., Xiao, Y., Wei, L., & Zhou, W. (2026) · Scientific Reports · doi:10.1038/s41598-026-37878-0 · Cited by 1
Combined ARHGEF6 and Tumor Mutational Burden may serve as a potential biomarker for immunotherapy of lung adenocarcinoma
Li, T., Wang, S., Yang, J., Zhang, Q., Gu, X., Mo, T., Luo, Y., Zhang, C., Zhang, J., & Liu, Y. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e18501 · Cited by 1
Efficacy of immunotherapy in patients with non-small cell lung cancer
Lyadova, M. A., Denisova, E. A., Fedorinov, D. S., Сергеевич, Е. Ю., Orlova, A. S., Vozniuk, D. A., Lyadov, K. V., & Галкин, В. Н. (2024) · Meditsinskiy sovet = Medical Council · doi:10.21518/ms2023-451 · Cited by 1
Inhibition of PD-L1 expression in non-small cell lung cancer may reduce vasculogenic mimicry formation by inhibiting the epithelial mesenchymal transformation process
Shi, Y., Li, W., Jia, Q., Wu, J., Wu, S., & Wu, S. (2024) · Experimental Cell Research · doi:10.1016/j.yexcr.2024.113996 · Cited by 1
The efficacy and safety of neoadjuvant treatment with the PD-1 inhibitor for locally advanced colorectal cancer: a meta-analysis
Yu, Y., Huang, L., Yan, R., Jiang, M., Li, S.-J., & Fan, W.-D. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1416943 · Cited by 1
CAR-T-Cell Therapy for Solid Tumors
Duggirala, S. (2025) · Springer eBooks · doi:10.1007/978-3-031-88695-9_6 · Cited by 1
Trilaciclib triggers a neutrophil-related immune response and sensitizes non-small cell lung cancer to anti-PD-1 therapy
Gao, Y., He, Y., Wang, C., Zuo, R., Tian, X., Zuo, D., Luo, Y., Liu, W., Feng, Y., Ling, A., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102434 · Cited by 1
The Effect of PD-1 Inhibitor Combined with Chemotherapy on the Level of Peripheral Blood T Lymphocytes among Patients with Non-Small-Cell Lung Cancer and Its Relationship with Prognosis
Zhao, Y., He, J., Zhou, S., Ning, R., Zhao, W., Wang, H., Su, C., Jiang, W., Xiaoning, Z., & Yu, Q. (2022) · Computational and Mathematical Methods in Medicine · doi:10.1155/2022/1679191 · Cited by 1
Identification of a polycomb group-related gene signature for predicting prognosis and immunotherapy efficacy in lung adenocarcinoma
Liu, L., Huang, Z., Zhang, P., Wang, W., Li, H., Sha, X., Wang, S., Zhou, Y. L., & Shi, J. (2023) · Journal of Thoracic Disease · doi:10.21037/jtd-22-1324 · Cited by 1
Efficacy of immune checkpoint inhibitors along with chemotherapy in non-small cell lung cancer and the impact on adverse reactions and serum tumor markers.
Xie, M., Wang, X., Wang, P., Liu, A., Wen, Y., & Xiao, B. (2023) · PubMed Central · Cited by 1
Sintilimab Plus Autologous NK Cells as Second-Line Treatment for Advanced Non-Small-Cell Lung Cancer Previous Treated with Platinum-Containing ChemotherapyPreprint
Cui, J., Jia, L., Chen, N., Chen, X., Niu, C. S., Liu, Z., Ma, K., Wang, N., Yang, L., Zhao, Y., et al. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4116417 · Cited by 1
COMBINATIONS OF IMMUNOTHERAPY AND OTHER DRUGS
Chubenko, V. A. (2021) · Practical oncology · doi:10.31917/2201033
PLXDC1 May Serve As A Target For Combining Antiangiogenic Therapy and Immunotherapy In Gastric AdenocarcinomaPreprint
Li, X., Fan, Y., Su, F., & Wang, Z. (2021) · Research Square · doi:10.21203/rs.3.rs-816727/v1
Who Will Benefit Most From PD-L1 Detection and Immunotherapy in Non-small Cell Lung Cancer?Preprint
Liu, L., Xie, B., Zhu, W., He, Q., Zhou, J., Liu, S., Tao, Y., & Xiao, D. (2021) · Research Square · doi:10.21203/rs.3.rs-1129762/v1
A Novel PD-L1-Containing MSLN Targeting Vaccine Elicits Therapeutic Antitumor Immunity in MicePreprint
Zeng, W., Pan, J., Huang, M., Fang, Z., Jia, J., Dong, J., Zhang, R., He, M., Zhong, H., He, J., et al. (2022) · Research Square · doi:10.21203/rs.3.rs-1545509/v1
Self-citation
Anti-PD-L1 Antibody Alleviate Pulmonary Fibrosis by Inducing Autophagy via Inhibition of the PI3K/Akt/mTOR PathwayPreprint
Lu, Y., Zhong, W., Liu, Y., Chen, W., Zhang, J., Zeng, Z., Huang, H., Qiao, Y., Wan, X., Meng, X., et al. (2021) · SSRN Electronic Journal · doi:10.2139/ssrn.3947644
Influence of concomitant gastric acid suppressants use on the survival of patients with non-small cell lung cancer treated with programmed death-1/ligand-1 inhibitors: A meta-analysis
Wang, M., Lu, D., & Bi, M. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.108955
An immune evasion molecular subgroup predicts prognosis in lung adenocarcinomaPreprint
lu, X., zhang, H., Zhang, Z., li, Z., Du, M., & Chen, B. (2022) · Research Square · doi:10.21203/rs.3.rs-2161529/v1
Correlation between prognostic indicator FGFR1 and immune infiltrates in non‑small cell lung cancerPreprint
Wang, X., Li, X., Liu, D., & Tang, Z. (2023) · Research Square · doi:10.21203/rs.3.rs-2421144/v1
Neoadjuvant anti-PD-1/PD-L1 therapy for colorectal cancer: Current status and future prospects
Han, Q., Zeng, H., Xu, W., & Wu, M. (2023) · World Chinese Journal of Digestology · doi:10.11569/wcjd.v31.i15.615
Comprehensive analysis of diverse programmed cell death patterns in the prognosis, tumor microenvironment and drug sensitivity in hepatocellular carcinoma
Yu, Y., Lou, Y., Zhu, J., & Wang, X. (2023) · Medicine · doi:10.1097/md.0000000000036239
Optimizing the spatial immune landscape of CD103+CD8+ tissue-resident memory T cells in non-small cell lung cancer by neoadjuvant chemotherapy
Yang, G., Hu, M., Cai, S., Li, C., Yang, L., Zhao, M., Jing, H., Xing, L., & Sun, X. (2024) · Cellular Oncology · doi:10.1007/s13402-024-00980-4
Research Progress on the Efficacy of Immune Checkpoint Inhibitor Combination Therapy in Advanced Non-Small Cell Lung Cancer
马, 普. (2025) · Hans Journal of Biomedicine · doi:10.12677/hjbm.2025.152030
KCTD10 promoting PD-L1 expression in colorectal cancer enhanced the anti-tumor effect of PD-1 antibody
Yin, Z., Su, R., Long, S., Chen, G., & Xiang, S. (2025) · Integrative Biology · doi:10.1093/intbio/zyaf014
The changes of CD47 and PD-L1 (SP142) before and after neoadjuvant therapy help predict prognosis of patients with stage IIIA-N2 non-small cell lung cancer
Jiang, Q., Lv, Y., Liu, Y., Gu, L., Wang, H., & Yang, Y. (2025) · International Journal of Clinical Oncology · doi:10.1007/s10147-025-02903-1
Additional file 2 of Single-cell RNA sequencing reveals enhanced antitumor immunity after combined application of PD-1 inhibitor and Shenmai injection in non-small cell lung cancer
Yu, D., Yang, P., Lu, X., Huang, S., Liu, L., & Fan, X. (2023) · Figshare · doi:10.6084/m9.figshare.23658108
Additional file 1 of Single-cell RNA sequencing reveals enhanced antitumor immunity after combined application of PD-1 inhibitor and Shenmai injection in non-small cell lung cancer
Yu, D., Yang, P., Lu, X., Huang, S., Liu, L., & Fan, X. (2023) · Figshare · doi:10.6084/m9.figshare.23658102
Additional file 1 of METTL14 regulates CD8+T-cell activation and immune responses to anti‐PD‐1 therapy in lung cancer
Sun, C., Wang, J., Li, H., Liu, L., Lin, Y., Zhang, L., Zu, X., Zhu, Y., Shu, Y., Shen, D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25792782
Integrative multi-omics and experimental validation identify histone acetylation-related genes BCL9L, STX10 and LSM7 as key mediators of PD-1-driven immune evasion and prognosis in non-small cell lung cancer
Zhou, J., Qiu, T., Hu, Z., Xiao, D., & Liu, Z. (2026) · International Immunopharmacology · doi:10.1016/j.intimp.2026.116424
Tageszeitenabhängige Immunchemotherapie bei nichtkleinzelligem Bronchialkarzinom: eine randomisierte Phase-3-Studie
Höffken, K. (2026) · Die Onkologie · doi:10.1007/s00761-026-01941-2
Whole-volume apparent diffusion coefficient histogram analysis for prediction of programmed cell death ligand 1 expression in periampullary carcinomas: a preliminary study
Bi, L., Xie, Q., Zhang, J.-T., Cai, S., Wang, X.-M., & Li, X. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1783525
Engineering a β-Sheet Enables Bispecific Binding in Single VHH Domains
Torres, S., Windsor, H. K., Beaudry, C., Girton, J., Cheung, N. T., Kuo, T.-H., Lobb, R. R., & Hackel, B. J. (2026) · ACS Synthetic Biology · doi:10.1021/acssynbio.6c00034
Antibody-based regimens targeting PD-1/PD-L1 and VEGF/VEGFR in advanced or metastatic NSCLC: a meta-analysis of RCTs
Mao, W., Tang, Z., Chen, Y., Chen, Y., Zhang, S., Feng, X., & Zhang, S. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1847913
A Mechanism-Guided Strategy by Weighting Key Reaction States for Rational Engineering of ω-Transaminase toward Bulky Chiral Amines
Yang, L., Sun, X., Yang, H., Zhao, W., Yuan, T., Wang, X., & Chen, F. (2026) · Organic Letters · doi:10.1021/acs.orglett.6c02236
Radiomics model based on pretreatment PET-CT imaging to predict response to sequential combination therapy of induction chemotherapy and radiotherapy in lung cancer: a multicenter retrospective study.
Lin, G., & Chi, Z. (2026) · Investigación Clínica · doi:10.54817/ic.v67n3a01
Heterogeneity in cancer: molecular mechanisms and therapeutic strategies
He, Y., Niu, L., Ren, Y.-M., Yuan, G.-Q., Pan, Y.-W., & Jin, W. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-03064-x
Discordance of PD-L1 expression between primary and paired metastatic non-small cell lung cancer: a systematic review and meta-analysis
Zhang, L., 高逸耀, Wang, X., Gu, Y., Hou, L., & Wang, X. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1942041

Authors: Huang, M.-Y., Jiang, X.-M., Wang, B.-L., Sun, Y., & Lu, J.-J.
Affiliations: University of Macau (MO)
State Key Laboratory of Pharmaceutical Biotechnology (CN)
Corresponding author: Lu, Jin-Jian
ORCID: Sun, Yang
Lu, Jin-Jian
Venue: Pharmacology & Therapeutics
Publisher: Elsevier BV
Published: 2021-03
Volume: 219
Pages: 107694
ISSN: 0163-7258 (ISSN-L)
DOI: 10.1016/j.pharmthera.2020.107694
OpenAlex: W3089009365
Cited by: 136
References: 142
Citations by year: 2026: 14 · 2025: 14 · 2024: 24 · 2023: 40 · 2022: 28 · 2021: 14
FWCI: 2.23
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Pharmacology & Therapeutics (publishedVersion)
PubMed (publishedVersion)
Funders: Universidade de Macau
National Natural Science Foundation of China
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
Keywords: PD-1/PD-L1 blockade, non-small cell lung cancer, combination therapy, cancer immunotherapy, combination chemotherapy, combination targeted therapy, immunotherapy resistance, cancer-immunity cycle, immune checkpoint inhibitors
MeSH terms: Carcinoma, Non-Small-Cell Lung, Humans, Immunotherapy, Lung Neoplasms, B7-H1 Antigen, Programmed Cell Death 1 Receptor

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Combination therapy with PD-1/PD-L1 blockade in non-small cell lung cancer: strategies and mechanisms

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks