Immune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy

Liu, Yuting; Zugazagoitia, Jon; Ahmed, Fahad Shabbir; Henick, Brian S.; Gettinger, Scott N.; Herbst, Roy S.; Schalper, Kurt A.; Rimm, David L.

doi:10.1158/1078-0432.ccr-19-1040

Cited by 324Cancer Immunotherapy and BiomarkersImmune cells in cancerFerroptosis and cancer prognosis

Immune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy

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Liu, Yuting, Zugazagoitia, Jon, Ahmed, Fahad Shabbir, Henick, Brian S., Gettinger, Scott N., Herbst, Roy S., Schalper, Kurt A., Rimm, David L.·2020·Clinical Cancer Research

DOI 10.1158/1078-0432.ccr-19-1040PMC PMC7024671

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Abstract

Purpose: Programmed death ligand 1 (PD-L1) is expressed in tumor cells and immune cells, and both have been associated with response to anti-PD-1 axis immunotherapy. Here, we examine the expression of PD-L1 to determine which cell type carries the predictive value of the test. Experimental Design: We measured the expression of PD-L1 in multiple immune cells with two platforms and confocal microscopy on three retrospective Yale NSCLC cohorts (425 nonimmunotherapy-treated cases and 62 pembrolizumab/nivolumab/atezolizumab-treated cases). The PD-L1 level was selectively measured in different immune cell subsets using two multiplexed quantitative immunofluorescence panels, including CD56 for natural killer cells, CD68 for macrophages, and CD8 for cytotoxic T cells. Results: PD-L1 was significantly higher in macrophages in both tumor and stromal compartment compared with other immune cells. Elevated PD-L1 in macrophages was correlated with high PD-L1 level in tumor as well as CD8 and CD68 level (P < 0.0001). High PD-L1 expression in macrophages was correlated with better overall survival (OS; P = 0.036 by cell count/P = 0.019 by molecular colocalization), while high PD-L1 expression in tumor cells was not. Conclusions: In nearly 500 non–small cell lung cancer (NSCLC) cases, the predominant immune cell type that expresses PD-L1 is CD68+ macrophages. The level of PD-L1 in macrophages is significantly associated with the level of PD-L1 in tumor cells and infiltration by CD8+ T cells, suggesting a connection between high PD-L1 and “hot” tumors. In anti-PD-1 axis therapy–treated patients, high levels of PD-L1 expression in macrophages are associated with longer OS and may be responsible for the predictive effect of the marker.

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Both PD-L1 expression and TMB fail to encapsulate various tumor microenvironmental features influencing ICI responses.
“However, both PDL-1 expression and TMB fail to encapsulate various tumor microenvironmental features influencing ICI responses15–17.”
From Predicting the tumor microenvironment composition and immunotherapy response in non-small cell lung cancer from digital histopathology images (2024) · cites this paper as [17]
The Introduction and Discussion (page numbers unavailable) show that which cells express PD-L1 matters for anti-PD-1 therapy; the Discussion reports an association between macrophage PD-L1 and survival in treated patients. This supports the concern that tumor-cell PD-L1 expression alone misses relevant microenvironmental features. The paper does not assess TMB or establish that TMB fails to capture those features. (LLM, conf=0.85)
Experimental — accuracy not yet measured
A previous study by Liu et al. revealed in NSCLC patients treated with ICI that only high PD-L1 expression in macrophages was correlated with better overall survival, while high PD-L1 expression in tumor or stromal cells was not.
“A previous study by Liu et al. highlighted an example of this complexity, revealing in NSCLC patients treated with ICI that only high PD-L1 expression in macrophages was correlated with better overall survival, while high PD-L1 expression in tumor or stromal cells was not17.”
From Predicting the tumor microenvironment composition and immunotherapy response in non-small cell lung cancer from digital histopathology images (2024) · cites this paper as [17]
The Results (page unavailable) report that, among immunotherapy-treated NSCLC patients, high PD-L1 in CD68+ macrophages was associated with better overall survival, whereas high PD-L1 in CK+ tumor cells was not. The paper does not report the claimed lack of an overall-survival association for PD-L1 in stromal cells as a separate group; indeed, its Results say most PD-L1-positive cells in the stromal compartment were macrophages. (LLM, conf=0.86)
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Tumor Immunology and Immunotherapy of Non-Small-Cell Lung CancerPreprint
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Upregulation of exosome secretion from tumor-associated macrophages plays a key role in the suppression of anti-tumor immunity
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Spatial signatures for predicting immunotherapy outcomes using multi-omics in non-small cell lung cancer
Aung, T. N., Monkman, J. H., Warrell, J., Vathiotis, I. A., Bates, K., Gavrielatou, N., Trontzas, I. P., Tan, C. W., Fernandez, A. I., Moutafi, M. K., et al. (2025) · Nature Genetics · doi:10.1038/s41588-025-02351-7 · Cited by 86 · see citing works
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The progress and challenge of anti-PD-1/PD-L1 immunotherapy in treating non-small cell lung cancer
Qu, J., Mei, Q., Liu, L., Cheng, T., Wang, P., Chen, L., & Zhou, J. (2021) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758835921992968 · Cited by 77 · see citing works
Quantitative Assessment of CMTM6 in the Tumor Microenvironment and Association with Response to PD-1 Pathway Blockade in Advanced-Stage Non–Small Cell Lung Cancer
Zugazagoitia, J., Liu, Y., Toki, M. I., McGuire, J., Ahmed, F. S., Henick, B. S., Gupta, R., Gettinger, S. N., Herbst, R. S., Schalper, K. A., et al. (2019) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2019.09.014 · Cited by 75 · see citing works
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Macrophage xCT deficiency drives immune activation and boosts responses to immune checkpoint blockade in lung cancer
Tang, B., Wang, Y., Xu, W., Zhu, J., Weng, Q., Chen, W., Fang, S., Yang, Y., Qiu, R., Chen, M., et al. (2022) · Cancer Letters · doi:10.1016/j.canlet.2022.216021 · Cited by 74 · see citing works
Insights into the Tumor Microenvironment—Components, Functions and Therapeutics
Baghy, K., Ladányi, A., Reszegi, A., & Kovalszky, I. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242417536 · Cited by 74 · see citing works
Extracellular matrix stiffness and tumor-associated macrophage polarization: new fields affecting immune exclusion
Yu, K.-X., Yuan, W.-J., Wang, H.-Z., & Li, Y. (2024) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-024-03675-9 · Cited by 78 · see citing works
Biomarkers in Precision Cancer Immunotherapy: Promise and Challenges
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Massive PD-L1 and CD8 double positive TILs characterize an immunosuppressive microenvironment with high mutational burden in lung cancer
Zhang, L., Chen, Y., Wang, H., Xu, Z., Wang, Y., Li, S., Liu, J., Chen, Y., Luo, H., Wu, L., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-002356 · Cited by 68 · see citing works
Down-regulation of the tumor suppressor miR-34a contributes to head and neck cancer by up-regulating the MET oncogene and modulating tumor immune evasion
Wu, X., Cheng, Y. L., Mathew, M., Yoon, A. J., Schwartz, G. K., Bala, S., Taylor, A. M., & Momen‐Heravi, F. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-01865-2 · Cited by 67 · see citing works
Mapping the Immune Landscape in Metastatic Melanoma Reveals Localized Cell–Cell Interactions That Predict Immunotherapy Response
Antoranz, A., Herck, Y. V., Bolognesi, M. M., Lynch, S. M., Rahman, A., Gallagher, W. M., Boecxstaens, V., Marine, J., Cattoretti, G., van den Oord, J. J., et al. (2022) · Cancer Research · doi:10.1158/0008-5472.can-22-0363 · Cited by 64 · see citing works
DENR controls JAK2 translation to induce PD-L1 expression for tumor immune evasion
Chen, B., Hu, J., Hu, X., Chen, H., Bao, R., Zhou, Y., Ye, Y., Zhan, M., Cai, W., Li, H., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29754-y · Cited by 60 · see citing works
The key to immunotherapy: how to choose better therapeutic biomarkers for patients with non-small cell lung cancer
Pan, Y., Fu, Y., Zeng, Y., Liu, X., Peng, Y., Hu, C., Deng, C., Qiu, Z., Zou, J. P., Liu, Y., et al. (2022) · Biomarker Research · doi:10.1186/s40364-022-00355-7 · Cited by 57 · see citing works
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Targeting immune checkpoints on tumor-associated macrophages in tumor immunotherapy
Xu, S., Wang, C., Yang, L., Wu, J., Li, M., Xiao, P., Xu, Z., Xu, Y., & Wang, K. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1199631 · Cited by 58 · see citing works
Reprogramming tumor-associated macrophages by a dually targeted milk exosome system as a potent monotherapy for cancer
Chen, Y., Gong, L., Cao, Y., Liu, Z., Wang, Y., Cheng, H. L. X. W., Feng, Y., Yao, S., Yin, Y., Wu, Z., et al. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.12.058 · Cited by 56 · see citing works
A PD-L1-targeting chimeric switch receptor enhances efficacy of CAR-T cell for pleural and peritoneal metastasis
Ma, Q., He, X., Zhang, B., Guo, F., Ou, X., Yang, Q., Shu, P., Chen, Y., Li, K., Gao, G., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01198-2 · Cited by 55 · see citing works
Tumor microenvironmental modification by the current target therapy for head and neck squamous cell carcinoma
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ALKBH5 promotes non-small cell lung cancer progression and susceptibility to anti-PD-L1 therapy by modulating interactions between tumor and macrophages
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Microglial reprogramming enhances antitumor immunity and immunotherapy response in melanoma brain metastases
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The PET-Tracer 89Zr-Df-IAB22M2C Enables Monitoring of Intratumoral CD8 T-cell Infiltrates in Tumor-Bearing Humanized Mice after T-cell Bispecific Antibody Treatment
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Macrophage and monocyte subsets as new therapeutic targets in cancer immunotherapy
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EGLIF-CAR-T Cells Secreting PD-1 Blocking Antibodies Significantly Mediate the Elimination of Gastric Cancer
Zhou, J.-T., Liu, J.-H., Song, T., Ma, B., Amidula, N., & Bai, C. (2020) · Cancer Management and Research · doi:10.2147/cmar.s260915 · Cited by 50 · see citing works
Macrophage secretory IL-1β promotes docetaxel resistance in head and neck squamous carcinoma via SOD2/CAT-ICAM1 signaling
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Modulation of miR-146b by N6-methyladenosine modification remodels tumor-associated macrophages and enhances anti-PD-1 therapy in colorectal cancer
He, S., Song, W., Cui, S., Li, J., Jiang, Y., Chen, X., & Peng, L. (2023) · Cellular Oncology · doi:10.1007/s13402-023-00839-0 · Cited by 47 · see citing works
Intravenous administration of BCG in mice promotes natural killer and T cell-mediated antitumor immunity in the lung
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A potential treatment option for transformed small-cell lung cancer on PD-L1 inhibitor-based combination therapy improved survival
Zhang, C., Sun, H., Su, J., Chen, Y., Zhang, S., Zheng, M.-Y., Li, Y., Huang, J., Zhang, C., Tai, Z., et al. (2022) · Lung Cancer · doi:10.1016/j.lungcan.2022.11.016 · Cited by 45 · see citing works
Multiplexed immunofluorescence identifies high stromal CD68+PD-L1+ macrophages as a predictor of improved survival in triple negative breast cancer
Wang, J., Browne, L. H., Šlapetová, I., Shang, F., Lee, K., Lynch, J., Beretov, J., Whan, R. M., Graham, P., & Millar, E. K. A. (2021) · Scientific Reports · doi:10.1038/s41598-021-01116-6 · Cited by 45 · see citing works
Combining Analysis of Tumor-infiltrating Lymphocytes (TIL) and PD-L1 Refined the Prognostication of Breast Cancer Subtypes
Ni, Y., Tsang, J. Y., Shao, Y., Poon, I. K., Tam, F. K. Y., Shea, K.-H., & Tse, G. M.-K. (2022) · The Oncologist · doi:10.1093/oncolo/oyab063 · Cited by 45 · see citing works
TMP195 Exerts Antitumor Effects on Colorectal Cancer by Promoting M1 Macrophages Polarization
Han, Y., Sun, J., Yang, Y., Liu, Y., Lou, J., Pan, H., Yao, J., & Han, W. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.73264 · Cited by 44 · see citing works
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Emerging diversity in extracellular vesicles and their roles in cancer
Sohal, I. S., & Kasinski, A. L. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1167717 · Cited by 43 · see citing works
Evolving insights into the improvement of adoptive T-cell immunotherapy through PD-1/PD-L1 blockade in the clinical spectrum of lung cancer
Li, Y., Sharma, A., & Schmidt‐Wolf, I. G. H. (2024) · Molecular Cancer · doi:10.1186/s12943-023-01926-4 · Cited by 43 · see citing works
Multi‐omic and spatial dissection of immunotherapy response groups in non‐small cell lung cancer
Monkman, J. H., Kim, H., Mayer, A. T., Mehdi, A. M., Matigian, N., Cumberbatch, M., Bhagat, M., Ladwa, R., Mueller, S. N., Adams, M. N., et al. (2023) · Immunology · doi:10.1111/imm.13646 · Cited by 42 · see citing works
GIS in Teacher Education - Facilitating GIS Applications in Secondary School Geography.
Johansson, T. (2003) · Cited by 42 · see citing works
Fibrotic immune microenvironment remodeling mediates superior anti-tumor efficacy of a nano-PD-L1 trap in hepatocellular carcinoma
Liu, X., Zhou, J., Wu, H., Chen, S., Zhang, L., Tang, W., Duan, L., Wang, Y., McCabe, E., Hu, M., et al. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.09.012 · Cited by 41 · see citing works
Comprehensive single-cell analysis demonstrates radiotherapy-induced infiltration of macrophages expressing immunosuppressive genes into tumor in esophageal squamous cell carcinoma
Oyoshi, H., Du, J., Sakai, S. A., Yamashita, R., Okumura, M., Motegi, A., Hojo, H., Nakamura, M., Hirata, H., Sunakawa, H., et al. (2023) · Science Advances · doi:10.1126/sciadv.adh9069 · Cited by 41 · see citing works
Sustained inhibition of CSF1R signaling augments antitumor immunity through inhibiting tumor-associated macrophages
Sato, T., Sugiyama, D., Koseki, J., Kojima, Y., Hattori, S., Sone, K., Nishinakamura, H., Ishikawa, T., Ishikawa, Y., Kato, T., et al. (2025) · JCI Insight · doi:10.1172/jci.insight.178146 · Cited by 41 · see citing works
Advanced insights on tumor-associated macrophages revealed by single-cell RNA sequencing: The intratumor heterogeneity, functional phenotypes, and cellular interactions
Yang, S., Wang, M., Hua, Y., Li, J., Zheng, H., Cui, M., Huang, N., Liu, Q., & Liao, Q. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216610 · Cited by 43 · see citing works
Spatial immunoprofiling of the intratumoral and peritumoral tissue of renal cell carcinoma patients
Brück, O. E., Lee, M. H., Turkki, R., Uski, I., Penttilä, P., Paavolainen, L., Kovanen, P. E., Järvinen, P., Bono, P., Pellinen, T. S., et al. (2021) · Modern Pathology · doi:10.1038/s41379-021-00864-0 · Cited by 40 · see citing works
Biomarkers for predicting the efficacy of immune checkpoint inhibitors
Wang, C., Wang, H.-N., & Wang, L. (2022) · Journal of Cancer · doi:10.7150/jca.65012 · Cited by 38 · see citing works
Tumor-associated macrophages in lymphoma: From mechanisms to therapy
Xiong, X., Xie, X., Wang, Z., Zhang, Y., & Wang, L. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109235 · Cited by 39 · see citing works
Spatial Analysis and Clinical Significance of HLA Class-I and Class-II Subunit Expression in Non–Small Cell Lung Cancer
Datar, I. J., Hauc, S. C., Desai, S., Gianino, N., Henick, B. S., Liu, Y., Syrigos, K., Rimm, D. L., Kavathas, P., Ferrone, S., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-3655 · Cited by 39 · see citing works
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Immune parameters associated with survival in metaplastic breast cancer
Chao, X., Liu, L., Sun, P., Yang, X., Li, M., Luo, R., Huang, Y., He, J., & Yun, J. (2020) · Breast Cancer Research · doi:10.1186/s13058-020-01330-6 · Cited by 38 · see citing works
The evolving landscape of predictive biomarkers in immuno‐oncology with a focus on spatial technologies
Sadeghirad, H., Bazaz, S. R., Monkman, J. H., Warkiani, M. E., Rezaei, N., O'Byrne, K. J., & Kulasinghe, A. (2020) · Clinical & Translational Immunology · doi:10.1002/cti2.1215 · Cited by 38 · see citing works
Assessing dynamic metabolic heterogeneity in non-small cell lung cancer patients via ultra-high sensitivity total-body [18F]FDG PET/CT imaging: quantitative analysis of [18F]FDG uptake in primary tumors and metastatic lymph nodes
Wang, D., Zhang, X., Liu, H., Qiu, B., Liu, S., Zheng, C., Fu, J., Mo, Y., Chen, N., Zhou, R., et al. (2022) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-022-05904-8 · Cited by 38 · see citing works
Predicting the tumor microenvironment composition and immunotherapy response in non-small cell lung cancer from digital histopathology images
Patkar, S., Chen, A., Basnet, A., Bixby, A., Rajendran, R., Chernet, R., Faso, S., Kumar, P. A., Desai, D., El-Zammar, O., et al. (2024) · npj Precision Oncology · doi:10.1038/s41698-024-00765-w · Cited by 41 · see citing works
“A previous study by Liu et al highlighted an example of this complexity, revealing in NSCLC patients treated with ICI that only high PD-L1 expression in macrophages was correlated with better overall survival, while high PD-L1 expression in tumor or stromal cells was not 39 .”
One cisplatin dose provides durable stimulation of anti-tumor immunity and alleviates anti-PD-1 resistance in an intraductal model for triple-negative breast cancer
Steenbrugge, J., Bellemans, J., Elst, N. V., Demeyere, K., Vliegher, J. D., Perera, T. P. S., Wever, O. D., Broeck, W. V. D., Spiegelaere, W. D., Sanders, N. N., et al. (2022) · OncoImmunology · doi:10.1080/2162402x.2022.2103277 · Cited by 36 · see citing works
Similar programmed death ligand 1 (PD-L1) expression profile in patients with mild COPD and lung cancer
Polverino, F., Mirra, D., Yang, C. X., Esposito, R., Spaziano, G., Rojas, J., Sgambato, M., Piegari, E., Cozzolino, A., Cione, E., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-26650-9 · Cited by 36 · see citing works
Reconnaissance of tumor immune microenvironment spatial heterogeneity in metastatic renal cell carcinoma and correlation with immunotherapy response
Hajiran, A. J., Chakiryan, N. H., Aydın, A. M., Zemp, L. W., Nguyen, J. V., Laborde, J. M., Chahoud, J., Spiess, P. E., Zaman, S., Falasiri, S. S. A., et al. (2020) · Clinical & Experimental Immunology · doi:10.1111/cei.13567 · Cited by 36 · see citing works
Low Infiltration of CD8+ PD-L1+ T Cells and M2 Macrophages Predicts Improved Clinical Outcomes After Immune Checkpoint Inhibitor Therapy in Non-Small Cell Lung Carcinoma
Li, L., Lu, G., Liu, Y., Gong, L., Zheng, X. Y., Zheng, H., Gu, W., & Yang, L. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.658690 · Cited by 35 · see citing works
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Bringing Macrophages to the Frontline against Cancer: Current Immunotherapies Targeting Macrophages
Reis-Sobreiro, M., da Mota, A. T., Jardim, C., & Serre, K. (2021) · Cells · doi:10.3390/cells10092364 · Cited by 37 · see citing works
Spatially multiplexed RNA in situ hybridization to reveal tumor heterogeneity
von Voithenberg, L. V., Khartchenko, A. F., Huber, D., Schraml, P., & Kaigala, G. V. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz1151 · Cited by 35 · see citing works
Targeting Tumor-Associated Macrophages in the Pediatric Sarcoma Tumor Microenvironment
Koo, J., Hayashi, M., Verneris, M. R., & Lee‐Sherick, A. B. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.581107 · Cited by 34 · see citing works
Overexpression of transposable elements is associated with immune evasion and poor outcome in colorectal cancer
Zhu, X., Fang, H., Gladysz, K., Barbour, J. A., & Wong, J. W. H. (2021) · European Journal of Cancer · doi:10.1016/j.ejca.2021.08.003 · Cited by 35 · see citing works
Immunomodulatory Properties of Immune Checkpoint Inhibitors—More than Boosting T-Cell Responses?
Kuske, M., Haist, M., Jung, T., Grabbe, S., & Bros, M. (2022) · Cancers · doi:10.3390/cancers14071710 · Cited by 36 · see citing works
Evolving perspectives regarding the role of the PD-1/PD-L1 pathway in gastric cancer immunotherapy
Yu, X., Zhai, X., Wu, J., Feng, Q., Hu, C., Zhu, L., & Zhou, Q. (2023) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2023.166881 · Cited by 34 · see citing works
Tumor-associated macrophages as a potential therapeutic target in thyroid cancers
Zhu, L., Li, X. J., Gangadaran, P., Jing, X., & Ahn, B. (2023) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-023-03549-6 · Cited by 34 · see citing works
PAD4 controls tumor immunity via restraining the MHC class II machinery in macrophages
Pitter, M. R., Kryczek, I., Zhang, H., Nagarsheth, N., Xia, H., Wu, Z., Tian, Y., Okła, K., Liao, P., Wang, W., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.113942 · Cited by 34 · see citing works
Classification of Non-Small Cell Lung Cancer’s Tumor Immune Micro-Environment and Strategies to Augment Its Response to Immune Checkpoint Blockade
Chi, A., He, X., Hou, L., Nguyen, N. P., Zhu, G., Cameron, R. B., & Lee, J. M. (2021) · Cancers · doi:10.3390/cancers13122924 · Cited by 35 · see citing works
Dynamic polarization of tumor-associated macrophages and their interaction with intratumoral T cells in an inflamed tumor microenvironment: from mechanistic insights to therapeutic opportunities
Han, J., Dong, L., Wu, M., & Ma, F. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1160340 · Cited by 35 · see citing works
Spatial proteomic profiling elucidates immune determinants of neoadjuvant chemo-immunotherapy in esophageal squamous cell carcinoma
Wu, C., Zhang, G., Wang, L., Hu, J., Ju, Z., Tao, H., Li, Q., Li, J., Zhang, W., Sheng, J., et al. (2024) · Oncogene · doi:10.1038/s41388-024-03123-z · Cited by 34 · see citing works
Response to immune checkpoint blockade improved in pre-clinical model of breast cancer after bariatric surgery
Sipe, L. M., Chaib, M., Korba, E. B., Jo, H., Lovely, M. C., Counts, B. R., Tanveer, U. A., Holt, J. R., Clements, J. C., John, N. A., et al. (2022) · eLife · doi:10.7554/elife.79143 · Cited by 32 · see citing works
Tumour-associated macrophages: versatile players in the tumour microenvironment
Ji, Z. Z., Chan, M. K., Chan, A. S. W., Leung, K. T., Jiang, X., To, K., Wu, Y., & Tang, P. M. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1261749 · Cited by 32 · see citing works
Exploring the role of the immune microenvironment in hepatocellular carcinoma: Implications for immunotherapy and drug resistance
Fu, Y., Guo, X., Sun, L., Cui, T., Wu, C., Wang, J., Liu, Y., & Liu, L. (2024) · eLife · doi:10.7554/elife.95009 · Cited by 31 · see citing works
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Programmed Death Ligand-1 (PD-L1) Is an Independent Negative Prognosticator in Western-World Gallbladder Cancer
Albrecht, T., Brinkmann, F., Albrecht, M. C., Lonsdorf, A. S., Mehrabi, A., Hoffmann, K., Kulu, Y., Charbel, A., Vogel, M. N., Rupp, C., et al. (2021) · Cancers · doi:10.3390/cancers13071682 · Cited by 31 · see citing works
SP140 inhibits STAT1 signaling, induces IFN-γ in tumor-associated macrophages, and is a predictive biomarker of immunotherapy response
Tanagala, K. K. K., Morin‐Baxter, J., Carvajal, R. D., Cheema, M., Dubey, S., Nakagawa, H., Yoon, A. J., Cheng, Y. L., Taylor, A. M., Nickerson, J. A., et al. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-005088 · Cited by 31 · see citing works
Role of Heterogeneous Nuclear Ribonucleoproteins in the Cancer-Immune Landscape
Sudhakaran, M., & Doseff, A. I. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065086 · Cited by 30 · see citing works
Characterization With KRAS Mutant Is a Critical Determinant in Immunotherapy and Other Multiple Therapies for Non-Small Cell Lung Cancer
Shen, M., Qi, R., Ren, J., Lv, D., & Yang, H. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2021.780655 · Cited by 29 · see citing works
Mass Cytometry Reveals Classical Monocytes, NK Cells, and ICOS+ CD4+ T Cells Associated with Pembrolizumab Efficacy in Patients with Lung Cancer
Rochigneux, P., Lisberg, A. E., Garcia, A. J., Granjeaud, S., Madroszyk, A., Fattori, S., Gonçalvès, A., Devillier, R., Maby, P., Salem, N., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-22-1386 · Cited by 29 · see citing works
Gallium-68–labeled Peptide PET Quantifies Tumor Exposure of PD-L1 Therapeutics
Mishra, A., Kumar, D., Gupta, K., Lofland, G., Sharma, A., Banka, D. S., Hobbs, R. F., Dannals, R. F., Rowe, S. P., Gabrielson, E. W., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-22-1931 · Cited by 29 · see citing works
LRP1B mutation is associated with tumor immune microenvironment and progression-free survival in lung adenocarcinoma treated with immune checkpoint inhibitors
He, Z., Feng, W., Wang, Y., Shi, L., Gong, Y., Shi, Y., Shen, S., & Huang, H. (2023) · Translational Lung Cancer Research · doi:10.21037/tlcr-23-39 · Cited by 28 · see citing works

Abstract 2674: Immune profiling of in NSCLC shows expression of PD-L1 in macrophages is better associated with outcomes than PD-L1 in tumor cells in PD-1 axis immunotherapy treated patients
Liu, Y., Zugazagoitia, J., Henick, B. S., Schalper, K. A., & Rimm, D. L. (2019) · Cancer Research · doi:10.1158/1538-7445.am2019-2674 · Cited by 1 · see citing works
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Abstract 2002: Assessment of the co-localization between PD-L1 positive macrophages and PD-1 positive cells is associated with benefit from PD-1 axis immunotherapy in NSCLC
Liu, Y., Zugazagoitia, J., Schalper, K. A., Herbst, R. S., & Rimm, D. L. (2020) · Cancer Research · doi:10.1158/1538-7445.am2020-2002
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Positive association between macrophage infiltration and PD-L1 expression in the tumor microenvironment
Cumberbatch, M., Memeo, L., Bhagat, M., Womack, C., & Kim, W. H. (2020) · European Journal of Cancer · doi:10.1016/s0959-8049(20)31246-6
PD-1 or PD-L1 co-localizes with immune cells for prediction of prognosis in non-small cell lung cancer.
Zhou, C., Lai, J., Chen, Y., Wang, Y., & Zhang, H. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.2020.38.15_suppl.e21029
Multiplex Immunohistochemistry Applies to Examination of PD-1/PD-L1 on Immune Cells for Prognosis Prediction in Non-Small Cell Lung CancerPreprint
Chen, H., Liao, H., Gong, L., Liu, J., Zhou, L., Kang, L., Zheng, H., & Wan, R. (2021) · Research Square · doi:10.21203/rs.3.rs-929708/v1

Authors: Liu, Y., Zugazagoitia, J., Ahmed, F. S., Henick, B. S., Gettinger, S. N., Herbst, R. S., Schalper, K. A., & Rimm, D. L.
Affiliations: Yale University (US)
Columbia University Irving Medical Center (US)
Corresponding author: Rimm, David L.
ORCID: Liu, Yuting
Zugazagoitia, Jon
Ahmed, Fahad Shabbir
Henick, Brian S.
Gettinger, Scott N.
Herbst, Roy S.
Schalper, Kurt A.
Rimm, David L.
Venue: Clinical Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2020-02-14
Volume: 26
Issue: 4
Pages: 970-977
ISSN: 1078-0432 (ISSN-L)
1557-3265
DOI: 10.1158/1078-0432.ccr-19-1040
PMC: PMC7024671
OpenAlex: W2980933209
Cited by: 322
References: 34
Citations by year: 2026: 23 · 2025: 28 · 2024: 65 · 2023: 59 · 2022: 64 · 2021: 50 · 2020: 25 · 2019: 2 · 2015: 1
FWCI: 14.73
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Clinical Cancer Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Yale SPORE in Lung Cancer (P50-CA196530)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
Keywords: PD-L1, tumor-associated macrophages, PD-1 pathway blockade, non-small cell lung cancer, pembrolizumab, nivolumab, atezolizumab, predictive biomarkers, CD8+ T cells, tumor immune microenvironment, overall survival
MeSH terms: Antineoplastic Agents, Immunological, Aged, Carcinoma, Non-Small-Cell Lung, Female, Humans, Killer Cells, Natural, Lung Neoplasms, Macrophages, Male, Neoplasm Staging, Retrospective Studies, Biomarkers, Tumor, Survival Rate, CD8-Positive T-Lymphocytes, B7-H1 Antigen, Programmed Cell Death 1 Receptor

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Immune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy

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