Cited by 114Cancer Immunotherapy and BiomarkersProtein Tyrosine PhosphatasesImmunotherapy and Immune Responses

The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.

SHP-2 and PD-L1 Inhibition Combined with Radiotherapy Enhances Systemic Antitumor Effects in an Anti–PD-1–Resistant Model of Non–Small Cell Lung Cancer

Open access

Chen, Dawei, Barsoumian, Hampartsoum B., Yang, Liangpeng, Younes, Ahmed I., Verma, Vivek, Hu, Yun, Menon, Hari, Wasley, Mark, Masropour, Fatemeh, Mosaffa, Sara, Ozgen, Tugce, Klein, Katherine, Cortez, Maria Angelica, Welsh, James W.·2020·Cancer Immunology Research

DOI 10.1158/2326-6066.cir-19-0744PMC PMC10173258

Published version of a preprint

Open this paper in CoChat — free account Open PDF

Abstract

Immune checkpoint inhibitors, such as anti–PD-1/PD-L1, have emerged as promising therapies for advanced non–small cell lung cancer (NSCLC). However, approximately 80% of patients do not respond to immunotherapy given alone because of intrinsic or acquired resistance. Radiotherapy (XRT) can overcome PD-1 resistance and improve treatment outcomes, but its efficacy remains suboptimal. The tyrosine phosphatase SHP-2, expressed in some cancers and in immune cells, has been shown to negatively affect antitumor immunity. Our hypothesis was that SHP-2 inhibition in combination with anti–PD-L1 would enhance immune-mediated responses to XRT and synergistically boost antitumor effects in an anti–PD-1–resistant mouse model. We treated 129Sv/Ev mice with anti–PD-1–resistant 344SQ NSCLC adenocarcinoma with oral SHP099 (a SHP-2 inhibitor) combined with XRT and intraperitoneal anti–PD-L1. Primary tumors were treated with XRT (three fractions of 12 Gy each), whereas abscopal (out-of-field) tumors were observed but not treated. XRT in combination with SHP099 and anti–PD-L1 promoted local and abscopal responses, reduced lung metastases, and improved mouse survival. XRT also increased SHP-2+ M1 tumor-associated macrophages in abscopal tumors (P = 0.019). The addition of SHP099 also associated with a higher M1/M2 ratio, greater numbers of CD8+ T cells, and fewer regulatory T cells. This triple-combination therapy had strong antitumor effects in a mouse model of anti–PD-1–resistant NSCLC and may be a novel therapeutic approach for anti–PD-1–resistant NSCLC in patients.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1158/2326-6066.cir-19-0744

Cites

38 of 38 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Cancer statistics, 2019
Siegel, R. L., Miller, K. D., & Jemal, A. (2019) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21551 · Cited by 20,160
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,320
Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer
Borghaei, H., Paz-Ares, L., Horn, L., Spigel, D. R., Steins, M., Ready, N. E., Chow, L. Q., Vokes, E. E., Felip, E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1507643 · Cited by 9,335
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
Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis
Wang, D. Y., Salem, J.-E., Cohen, J. V., Chandra, S., Menzer, C., Ye, F., Zhao, S., Das, S., Beckermann, K. E., Ha, L., et al. (2018) · JAMA Oncology · doi:10.1001/jamaoncol.2018.3923 · Cited by 2,674
PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity
Gordon, S. R., Maute, R. L., Dulken, B. W., Hutter, G., George, B. M., McCracken, M. N., Gupta, R., Tsai, J. M., Sinha, R., Corey, D., et al. (2017) · Nature · doi:10.1038/nature22396 · Cited by 2,247
The Tumour Microenvironment after Radiotherapy: Mechanisms of Resistance and Recurrence
Barker, H. E., Paget, J. T. E., Khan, A. A., & Harrington, K. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3958 · Cited by 2,144
Irradiation and anti–PD-L1 treatment synergistically promote antitumor immunity in mice
Deng, L., Liang, H. L., Burnette, B., Beckett, M., Darga, T. E., Weichselbaum, R. R., & Fu, Y. (2014) · Journal of Clinical Investigation · doi:10.1172/jci67313 · Cited by 2,119
T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition
Hui, E., Cheung, J., Zhu, J., Su, X., Taylor, M. J., Wallweber, H. A., Sasmal, D. K., Huang, J., Kim, J. M., Mellman, I., et al. (2017) · Science · doi:10.1126/science.aaf1292 · Cited by 1,689

Show all 38 references

Sorted by citations

Combination strategies with PD-1/PD-L1 blockade: current advances and future directions
Yi, M., Zheng, X., Niu, M., Zhu, S., Ge, H., & Wu, K. (2022) · Molecular Cancer · doi:10.1186/s12943-021-01489-2 · Cited by 1,445
Research progress of therapeutic effects and drug resistance of immunotherapy based on PD-1/PD-L1 blockade
Pang, K., Shi, Z., Wei, L., Yang, D. F., Ma, Y.-Y., Wang, W., Wang, G.-Y., Cao, M.-Y., Dong, J., Chen, Y.-A., et al. (2022) · Drug Resistance Updates · doi:10.1016/j.drup.2022.100907 · Cited by 268
Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders
Stanford, S. M., & Bottini, N. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00618-w · Cited by 139
A comprehensive review of SHP2 and its role in cancer
Asmamaw, M. D., Shi, X.-J., Zhang, L.-R., & Liu, H.-M. (2022) · Cellular Oncology · doi:10.1007/s13402-022-00698-1 · Cited by 119
Strategies Targeting Protein Tyrosine Phosphatase SHP2 for Cancer Therapy
Song, Y., Wang, S., Zhao, M., Yang, X., & Yu, B. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c02008 · Cited by 101
High-dose irradiation in combination with non-ablative low-dose radiation to treat metastatic disease after progression on immunotherapy: Results of a phase II trial
Patel, R. R., He, K., Barsoumian, H. B., Chang, J. Y., Tang, C. Z., Verma, V., Comeaux, N. I., Chun, S. G., Gandhi, S. J., Truong, M. T., et al. (2021) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2021.06.037 · Cited by 105
Self-citation
SHP-2 and PD-1-SHP-2 signaling regulate myeloid cell differentiation and antitumor responses
Christofides, A., Katopodi, X.-L., Cao, C., Karagkouni, D., Aliazis, K., Yenyuwadee, S., Aksoylar, H., Pal, R., Mahmoud, M. A. A., Strauss, L., et al. (2022) · Nature Immunology · doi:10.1038/s41590-022-01385-x · Cited by 96
Melatonin enhances radiofrequency-induced NK antitumor immunity, causing cancer metabolism reprogramming and inhibition of multiple pulmonary tumor development
Li, M., Hao, B., Zhang, M., Reiter, R. J., Lin, S., Zheng, T., Chen, X., Ren, Y., Yue, L., Abay, B., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00745-7 · Cited by 71
Pivotal roles of tumor‐draining lymph nodes in the abscopal effects from combined immunotherapy and radiotherapy
Liu, Z., Yu, Z., Chen, D., Verma, V., Yuan, C., Wang, M., Wang, F., Fan, Q., Wang, X., Li, Y., et al. (2022) · 癌症：英文版 · doi:10.1002/cac2.12348 · Cited by 69
Self-citation
Durvalumab and tremelimumab with or without stereotactic body radiation therapy in relapsed small cell lung cancer: a randomized phase II study
Pakkala, S., Higgins, K. A., Chen, Z., Sica, G., Steuer, C. E., Zhang, C., Zhang, G., Wang, S., Hossain, M. S., Nazha, B., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-001302 · Cited by 68
Strategies to overcome drug resistance using SHP2 inhibitors
Liu, M., Gao, S., Elhassan, R. M., Hou, X., & Fang, H. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.03.037 · Cited by 58
Molecular features underlying differential SHP1/SHP2 binding of immune checkpoint receptors
Xu, X., Masubuchi, T., Cai, Q., Zhao, Y., & Hui, E. (2021) · eLife · doi:10.7554/elife.74276 · Cited by 59
Inhibition of STAT6 with Antisense Oligonucleotides Enhances the Systemic Antitumor Effects of Radiotherapy and Anti–PD-1 in Metastatic Non–Small Cell Lung Cancer
He, K., Barsoumian, H. B., Puebla‐Osorio, N., Hu, Y. Y., Sezen, D., Wasley, M. D., Bertolet, G., Zhang, J., Leuschner, C., Yang, L., et al. (2023) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-22-0547 · Cited by 58
Self-citation
ALKBH5 promotes non-small cell lung cancer progression and susceptibility to anti-PD-L1 therapy by modulating interactions between tumor and macrophages
Hua, X., Xu, Q., Wu, R., Sun, W., Gu, Y., Zhu, S., Liu, X., Lv, T., & Song, Y. (2024) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-024-03073-0 · Cited by 53
PAI-1-driven SFRP2high cancer-associated fibroblasts hijack the abscopal effect of radioimmunotherapy
Zhang, Y.-P., Guo, Z.-Q., Cai, X.-T., Rong, Z.-X., Fang, Y., Chen, J., Zhuang, K., Ruan, M.-J., Ma, S.-C., Lin, L.-Y., et al. (2025) · Cancer Cell · doi:10.1016/j.ccell.2025.02.024 · Cited by 58
The abscopal effect: a sense of DNA damage is in the air
Lippert, T. P., & Greenberg, R. A. (2021) · Journal of Clinical Investigation · doi:10.1172/jci148274 · Cited by 53
Enhanced anti-PD-1 therapy in hepatocellular carcinoma by tumor vascular disruption and normalization dependent on combretastatin A4 nanoparticles and DC101
Bao, X., Shen, N., Lou, Y., Yu, H., Wang, Y., Liu, L., Tang, Z., & Chen, X. (2021) · Theranostics · doi:10.7150/thno.58164 · Cited by 47
Opportunities for improving brain cancer treatment outcomes through imaging-based mathematical modeling of the delivery of radiotherapy and immunotherapy
Hormuth, D. A., Farhat, M., Christenson, C., Curl, B. J., Quarles, C. C., Chung, C. D., & Yankeelov, T. E. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114367 · Cited by 45
Modulation of TCR Signaling by Tyrosine Phosphatases: From Autoimmunity to Immunotherapy
Castro-Sanchez, P., Teagle, A. R., Prade, S., & Zamoyska, R. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.608747 · Cited by 44
Anti-PD-1/Anti-PD-L1 Drugs and Radiation Therapy: Combinations and Optimization Strategies
Boustani, J., Lecoester, B., Baude, J., Latour, C., Adotévi, O., Mirjolet, C., & Truc, G. (2021) · Cancers · doi:10.3390/cancers13194893 · Cited by 44
The PD‐1 Interactome
Wang, Q., Bardhan, K., Boussiotis, V. A., & Patsoukis, N. (2021) · Advanced Biology · doi:10.1002/adbi.202100758 · Cited by 39
Research Progress of Anti-PD-1/PD-L1 Immunotherapy Related Mechanisms and Predictive Biomarkers in NSCLC
Bie, F., Tian, H., Sun, N., Zang, R., Zhang, M., Song, P., Liu, L., Peng, Y., Bai, G., Zhou, B., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.769124 · Cited by 39
Crystallographic landscape of SHP2 provides molecular insights for SHP2 targeted drug discovery
Song, Y., Yang, X., Wang, S., Zhao, M., & Yu, B. (2022) · Medicinal Research Reviews · doi:10.1002/med.21890 · Cited by 35
Targeting the Macrophage-Ferroptosis Crosstalk: A Novel Insight into Tumor Immunotherapy
Zhou, Z., Xu, B., Hu, N., Guo, Z., Bao, W., Shao, B., & Yang, W. (2022) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2707203 · Cited by 37
Small molecule inhibitors for cancer immunotherapy and associated biomarkers – the current status
Schlicher, L., Green, L. G., Romagnani, A., & Renner, F. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1297175 · Cited by 34
Critical roles of PTPN family members regulated by non-coding RNAs in tumorigenesis and immunotherapy
Tang, X., Qi, C., Zhou, H., & Liu, Y. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.972906 · Cited by 33
Combination Approaches to Target PD-1 Signaling in Cancer
Moore, E. K., Strazza, M., & Mor, A. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.927265 · Cited by 32
A combination of PD‑1/PD‑L1 inhibitors: The prospect of overcoming the weakness of tumor immunotherapy (Review)
Kong, X., Lü, P., Liu, C., Guo, Y., Yang, Y., Peng, Y., Wang, F., Zhang, B., Dou, X., Shi, H., et al. (2021) · Molecular Medicine Reports · doi:10.3892/mmr.2021.12001 · Cited by 30
Molecular mechanisms underlying the abscopal effect induced by radiotherapy and its synergistic translational potential with immunotherapy
Chen, X., Yang, M., Huang, Y., Tu, J., Cai, Y., & Yuan, X. (2025) · Therapeutic Advances in Medical Oncology · doi:10.1177/17588359251387534 · Cited by 29
Targeting tumor microenvironment for non-small cell lung cancer immunotherapy
Wang, L., Jia, Q., Chu, Q., & Zhu, B. (2023) · Chinese Medical Journal - Pulmonary and Critical Care Medicine · doi:10.1016/j.pccm.2022.11.001 · Cited by 30
Biology of NSCLC: Interplay between Cancer Cells, Radiation and Tumor Immune Microenvironment
Tubin, S., Khan, M. K., Gupta, S., & Jeremic, B. M. (2021) · Cancers · doi:10.3390/cancers13040775 · Cited by 25
Radiation dose and schedule influence the abscopal effect in a bilateral murine CT26 tumor model
Nazari, H. G., Alimohammadi, M., Alimohammadi, R., Rostami, E., Bakhshandeh, M., Webster, T. J., Chalbatani, G. M., Tavakkol‐Afshari, J., & Jalali, S. A. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.108737 · Cited by 24
Advances in SHP2 tunnel allosteric inhibitors and bifunctional molecules
Guo, Z., Duan, Y., Sun, K., Zheng, T., Liu, J., Xu, S., & Xu, J. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116579 · Cited by 26
Radiotherapy, photodynamic therapy, and cryoablation‐induced abscopal effect: Challenges and future prospects
Mohammad, S. A., Hak, A., Pogu, S. V., & Rengan, A. K. (2023) · Cancer Innovation · doi:10.1002/cai2.53 · Cited by 20
NLRP3 agonist enhances radiation-induced immune priming and promotes abscopal responses in anti-PD1 resistant model
Barsoumian, H. B., He, K., Hsu, E. Y., Bertolet, G., Sezen, D., Hu, Y. Y., Riad, T. S., Cortez, M. A., & Welsh, J. W. (2023) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-023-03471-x · Cited by 21
Self-citation
Tumor-associated macrophages affect the treatment of lung cancer
Yu, Z., Zou, J., & Xu, F. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e29332 · Cited by 22
Overexpression of ESYT3 improves radioimmune responses through activating cGAS-STING pathway in lung adenocarcinoma
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Experimental Hematology and Oncology · doi:10.1186/s40164-024-00546-y · Cited by 18
Local Destruction of Tumors and Systemic Immune Effects
Tranberg, K. ‐. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.708810 · Cited by 17
Progress in the clinical application of immune checkpoint inhibitors in small cell lung cancer
He, J., & Hu, Q. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1126582 · Cited by 15
ExoPD-L1: an assistant for tumor progression and potential diagnostic marker
Hu, R. H., Jahan, M. S., & Tang, L. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1194180 · Cited by 14
Enhanced tumor control and survival in preclinical models with adoptive cell therapy preceded by low-dose radiotherapy
Puebla‐Osorio, N., Fowlkes, N. W., Barsoumian, H. B., Xega, K., Srivastava, G., Kettlun-Leyton, C., Nizzero, S., Voss, T. A., Riad, T. S., Wong, C., et al. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1407143 · Cited by 14
Self-citation
Identification of TUBB3 as an immunotherapy target in lung cancer by genome wide in vivo CRISPR screening
Zhao, D., Deshpande, R. P., Wu, K., Tyagi, A., Sharma, S., Wu, S.-Y., Xing, F., O’Neill, S. S., Ruiz, J., Lyu, F., et al. (2024) · Neoplasia · doi:10.1016/j.neo.2024.101100 · Cited by 13
Targeting SHP2 Signaling in Lung Cancer
Imbody, D. J., Arce-Ruiz, K. M., Solanki, H. S., Haura, E. B., & Pellini, B. (2023) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2023.08.009 · Cited by 12
Spatial interaction and functional status of CD68+SHP2+ macrophages in tumor microenvironment correlate with overall survival of NSCLC
Liu, X., Zhang, Z., Yuan, J., Yu, J., & Chen, D. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1396719 · Cited by 13
Self-citation
Mechanism of exosomes in the tumor microenvironment in the abscopal effect (Review)
Kuang, G., Wang, Z., Luo, C., Luo, J., & Wang, J. (2022) · International Journal of Oncology · doi:10.3892/ijo.2022.5450 · Cited by 11
Complex Roles of PTPN11/SHP2 in Carcinogenesis and Prospect of Targeting SHP2 in Cancer Therapy
Scheiter, A., Lu, L., Gao, L. H., & Feng, G. (2023) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-062722-013740 · Cited by 13
Efficacy of immune checkpoint inhibitors for NSCLC in patients with different age: A systematic review and meta-analysis
Zhang, Q., Liang, X., Wang, Z., Sun, A., Cao, T.-B., Zhang, Y.-P., Li, N., Yi, T., & Qu, K. (2024) · Asian Journal of Surgery · doi:10.1016/j.asjsur.2024.03.145 · Cited by 12
Radiotherapy combined with immunotherapy could improve the immune infiltration of melanoma in mice and enhance the abscopal effect
Zheng, Y., Liu, X., Li, N., Zhao, A., Sun, Z., Wang, M., & Luo, J. (2023) · Radiation Oncology Journal · doi:10.3857/roj.2023.00185 · Cited by 11
Oncological Response and Predictive Biomarkers for the Checkpoint Inhibitors in Castration-Resistant Metastatic Prostate Cancer: A Systematic Review and Meta-Analysis
Fahmy, O., Alhakamy, N. A., Khairul‐Asri, M. G., Ahmed, O. A. A., Fahmy, U. A., Fresta, C. G., & Caruso, G. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm12010008 · Cited by 11
Tumor Cell–Autonomous SHP2 Contributes to Immune Suppression in Metastatic Breast Cancer
Chen, H., Cresswell, G. M., Libring, S., Ayers, M. G., Miao, J., Zhang, Z., Solorio, L., Ratliff, T. L., & Wendt, M. K. (2022) · Cancer Research Communications · doi:10.1158/2767-9764.crc-22-0117 · Cited by 9
The RadScopal Technique as an Immune Adjuvant to Treat Cancer
Barsoumian, H. B., Hsu, J., Nanez, S., Hu, Y. Y., Hsu, E. Y., Riad, T. S., Puebla‐Osorio, N., Cortez, M. A., & Welsh, J. W. (2023) · Immuno · doi:10.3390/immuno3010006 · Cited by 9
Self-citation
βhCG mediates immune suppression through upregulation of CD11b +Gr1+ myeloid derived suppressor cells, CD206 + M2 macrophages, and CD4 + FOXP3 + regulatory T‐cells in BRCA1 deficient breast cancers
Varghese, G. R., Patra, D., Jaikumar, V. S., Rajan, A., Latha, N. R., & Srinivas, P. (2023) · Immunology · doi:10.1111/imm.13673 · Cited by 8
Genomic data from NSCLC tumors reveals correlation between SHP-2 activity and PD-L1 expression and suggests synergy in combining SHP-2 and PD-1/PD-L1 inhibitors
Toral, K., Wuenschel, M. A., & Black, E. P. (2021) · PLoS ONE · doi:10.1371/journal.pone.0256416 · Cited by 8
Rocaglamide promotes infiltration and differentiation of T cells and coordinates with PD-1 inhibitor to overcome checkpoint resistance in multiple tumor models
Luo, J., Ng, W., Liu, Y., Wang, L., Gong, C., Zhou, Y., Cheng, F., Zhu, S., & Yao, C. (2024) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-024-03706-5 · Cited by 7
PD-L1/SHP2 dual PROTACs inhibit melanoma by enhancing T-cell killing activity
Liu, Y., Liang, J., Zheng, M., Song, H., Chen, L., & Li, H. (2024) · Chinese Chemical Letters · doi:10.1016/j.cclet.2024.110317 · Cited by 8
Anti-Tumor Potential of Post-Translational Modifications of PD-1
Xi, X., & Zhao, W. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46030136 · Cited by 6
Targeting SHP2 sensitizes differentiated thyroid carcinoma to the MEK inhibitor.
Zhi, J., Yi, J., Hou, X., Wang, W., Yang, W., Hu, L., Huang, J., Guo, S., Ruan, X., Gao, M., et al. (2022) · PubMed Central · Cited by 6
Identification and verification of PTPN3 as a novel biomarker in predicting cancer prognosis, immunity, and immunotherapeutic efficacy
Zhou, Z., Lin, Z., Wang, M., Wang, L., Ji, Y., Yang, J., Yang, Y., Zhu, G., & Liu, T. (2024) · European journal of medical research · doi:10.1186/s40001-023-01587-5 · Cited by 6
Discovery of novel substituted pyridine carboxamide derivatives as potent allosteric SHP2 inhibitors
Lv, X., Li, P., Chen, Z., Huang, S., Zhang, S., Ji, B., Liu, J., Du, T., Zhang, T., Chen, X., et al. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116830 · Cited by 4
Study on the allosteric activation mechanism of SHP2 via elastic network models and neural relational inference molecular dynamics simulation
Liu, L., Cheng, Y., Zhang, Z., Li, J., Geng, Y., Li, Q., Luo, D., Liang, L., Liu, W., Hu, J., et al. (2023) · Physical Chemistry Chemical Physics · doi:10.1039/d3cp02795c · Cited by 5
PD-1 agonist: A novel therapeutic approach to resolve atherosclerosis
Chen, J., Yu, W., Liao, L., Fu, L., & Yang, P. (2024) · Results in Chemistry · doi:10.1016/j.rechem.2024.101892 · Cited by 5
Metabolism of Tryptophan, Glutamine, and Asparagine in Cancer Immunotherapy—Synergism or Mechanism of Resistance?
Kiełbowski, K., Bakinowska, E., Becht, R., & Pawlik, A. (2025) · Metabolites · doi:10.3390/metabo15030144 · Cited by 5
The clinical significance and potential therapeutic target of tumor-associated macrophage in non-small cell lung cancer
Sun, J., Zhou, S., Sun, Y., & Zeng, Y. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1541104 · Cited by 4
Immunotherapy and radiotherapy: An effective combination in cancer treatment
Li, X., Wang, C., Yang, H., Xue, W., Ding, Y.-Q., Wu, N., Pei, B., Ma, X., & Yang, W. (2025) · Chinese Medical Journal · doi:10.1097/cm9.0000000000003609 · Cited by 5
Combining radiation with immune checkpoint inhibitors therapy for HCC: From the alteration of the immune microenvironment by radiotherapy
Zhou, K., Jiang, Y., Feng, S., Wang, T.-Y., Wang, L., Cao, J., & Jiao, Y. (2022) · Radiation Medicine and Protection · doi:10.1016/j.radmp.2022.07.005 · Cited by 4
The value of intervention with radiotherapy after first-line chemo-immunotherapy in locally advanced or metastatic esophageal squamous cell carcinoma: A multi-center retrospective study
Hu, H., Xu, X., Li, X., Zeng, Y., Li, Y., Song, X., Fu, X., Ma, X., & Yu, W. (2024) · Clinical and Translational Radiation Oncology · doi:10.1016/j.ctro.2024.100818 · Cited by 4
Protein tyrosine phosphatase non-receptor II: A possible biomarker of poor prognosis and mediator of immune evasion in hepatocellular carcinoma
Li, H., Jing, Y.-M., Xue, S., Tang, M., Shen, H., Li, X., Wang, Z., & Su, F. (2024) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v16.i9.3913 · Cited by 4
Dissecting Immunotherapy Strategies for Small Cell Lung Cancer: Antibodies, Ionizing Radiation and CAR-T
Guaitoli, G., Neri, G., Cabitza, E., Natalizio, S., Mastrodomenico, L., Talerico, S., Trudu, L., Lauro, C., Chiavelli, C., Baschieri, M. C., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232112728 · Cited by 4
Synergistic blockade of SHP-2 and A2AR signal pathways with targeted nanoparticles restores anti-tumor immunity of CD8+ T cells
Chen, M., Zhang, L., Lin, W., Zhou, Z., Wang, Y., Wang, L., Gu, H., Li, J., & Xu, Z. P. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.113889 · Cited by 3
Anti-PD-L1 antibody retains antitumour effects while mitigating immunotherapy-related colitis in bladder cancer-bearing mice after CT-mediated intratumoral delivery
Wang, Y.-S., Zheng, A.-H., Zhao, J., Gu, H.-Y., Meng, Z.-N., Chen, J.-Y., Wang, F.-W., Zhu, X.-M., Chen, Y., Xu, S.-C., et al. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.112417 · Cited by 2
Roles of the phagocytosis checkpoint in radiotherapy
Kui, Y., Tong, F., Zhang, R., Wang, J., & Dong, X. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07921-5 · Cited by 1
Tumor cell-intrinsic PD-1 in malignant ascites drives ovarian cancer progression via MAPK/ERK signaling
Xu, J., Shi, G., Qin, Z., Yin, B., Qiu, Y., Yu, Y., Zhang, H., He, J., Su, D., Zhang, Y., et al. (2026) · Oncogene · doi:10.1038/s41388-026-03693-0 · Cited by 1
Dual Functions of Treg in the Mucosal Barrier and Lung Cancer Microenvironment and Prospects for Targeted Therapy
Cui, J., Han, J., Dai, Y., Li, S., Wang, X., Ge, T., He, G., Zhou, J., Yang, L., Tian, Y., et al. (2026) · Immunology · doi:10.1111/imm.70140 · Cited by 1
Self-citation
Precision Medicine in Immunoradiotherapy
Feng, J., Peng, J., Qiu, H., Hu, K., Guo, X., Liu, B., Bu, L., & Wu, Q. (2025) · Springer eBooks · doi:10.1007/978-981-96-3659-4_11 · Cited by 1
Hub Gene Screening and Prognostic Modeling of Lung Cancer: An Integrated Bioinformatics Study
Bai, H., & Huang, X. (2022) · Computational and Mathematical Methods in Medicine · doi:10.1155/2022/5110683 · Cited by 1
Retracted
Discovery of Novel Substituted Pyridine Carboxamide Derivatives as Potent and Selective Shp2 Allosteric InhibitorsPreprint
Lv, X., Li, P., Chen, Z., Huang, S., Du, T., Ji, B., Zhang, S., Liu, J., Zhang, T., Chen, X., et al. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4871858
Investigating the anticancer properties of six benzothiazolopyrimidine derivatives on colon carcinoma cells, in vitro and in vivo
Bakharzi, M., Attar, E., Garmabi, H., Esmaeili, A. A., Bahrami, A. R., Danehchin, M., & Matin, M. M. (2024) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.23779
Paired CRISPR screens to map gene regulation in cis and transPreprint
Xue, X., Gajic, Z. Z., Caragine, C. M., Legut, M., Walker, C. R., Kim, J. Y. S., Wang, X., Yan, R., Wessels, H., Lu, C., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.11.27.625752
Additional file 8 of ALKBH5 promotes non-small cell lung cancer progression and susceptibility to anti-PD-L1 therapy by modulating interactions between tumor and macrophages
Hua, X., Xu, Q., Wu, R., Sun, W., Gu, Y., Zhu, S., Liu, X., Lv, T., & Song, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26733735
Additional file 5 of ALKBH5 promotes non-small cell lung cancer progression and susceptibility to anti-PD-L1 therapy by modulating interactions between tumor and macrophages
Hua, X., Xu, Q., Wu, R., Sun, W., Gu, Y., Zhu, S., Liu, X., Lv, T., & Song, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26733726
Additional file 13 of Overexpression of ESYT3 improves radioimmune responses through activating cGAS-STING pathway in lung adenocarcinoma
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757907
Additional file 9 of ALKBH5 promotes non-small cell lung cancer progression and susceptibility to anti-PD-L1 therapy by modulating interactions between tumor and macrophages
Hua, X., Xu, Q., Wu, R., Sun, W., Gu, Y., Zhu, S., Liu, X., Lv, T., & Song, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26733738
Additional file 4 of Overexpression of ESYT3 improves radioimmune responses through activating cGAS-STING pathway in lung adenocarcinoma
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757877
Additional file 12 of Overexpression of ESYT3 improves radioimmune responses through activating cGAS-STING pathway in lung adenocarcinoma
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757904
Additional file 8 of Overexpression of ESYT3 improves radioimmune responses through activating cGAS-STING pathway in lung adenocarcinoma
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757889
Additional file 7 of ALKBH5 promotes non-small cell lung cancer progression and susceptibility to anti-PD-L1 therapy by modulating interactions between tumor and macrophages
Hua, X., Xu, Q., Wu, R., Sun, W., Gu, Y., Zhu, S., Liu, X., Lv, T., & Song, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26733732
Additional file 14 of Overexpression of ESYT3 improves radioimmune responses through activating cGAS-STING pathway in lung adenocarcinoma
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757910
Additional file 3 of ALKBH5 promotes non-small cell lung cancer progression and susceptibility to anti-PD-L1 therapy by modulating interactions between tumor and macrophages
Hua, X., Xu, Q., Wu, R., Sun, W., Gu, Y., Zhu, S., Liu, X., Lv, T., & Song, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26733720
Additional file 11 of Overexpression of ESYT3 improves radioimmune responses through activating cGAS-STING pathway in lung adenocarcinoma
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757901
Additional file 7 of Overexpression of ESYT3 improves radioimmune responses through activating cGAS-STING pathway in lung adenocarcinoma
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757886
Additional file 1 of Overexpression of ESYT3 improves radioimmune responses through activating cGAS-STING pathway in lung adenocarcinoma
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26500319
Additional file 2 of ALKBH5 promotes non-small cell lung cancer progression and susceptibility to anti-PD-L1 therapy by modulating interactions between tumor and macrophages
Hua, X., Xu, Q., Wu, R., Sun, W., Gu, Y., Zhu, S., Liu, X., Lv, T., & Song, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26733717
Additional file 5 of Overexpression of ESYT3 improves radioimmune responses through activating cGAS-STING pathway in lung adenocarcinoma
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757880
Additional file 16 of Overexpression of ESYT3 improves radioimmune responses through activating cGAS-STING pathway in lung adenocarcinoma
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757916
Additional file 1 of ALKBH5 promotes non-small cell lung cancer progression and susceptibility to anti-PD-L1 therapy by modulating interactions between tumor and macrophages
Hua, X., Xu, Q., Wu, R., Sun, W., Gu, Y., Zhu, S., Liu, X., Lv, T., & Song, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26733714
Additional file 3 of Overexpression of ESYT3 improves radioimmune responses through activating cGAS-STING pathway in lung adenocarcinoma
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757874
Additional file 10 of Overexpression of ESYT3 improves radioimmune responses through activating cGAS-STING pathway in lung adenocarcinoma
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757895
Additional file 17 of Overexpression of ESYT3 improves radioimmune responses through activating cGAS-STING pathway in lung adenocarcinoma
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757919
Additional file 6 of ALKBH5 promotes non-small cell lung cancer progression and susceptibility to anti-PD-L1 therapy by modulating interactions between tumor and macrophages
Hua, X., Xu, Q., Wu, R., Sun, W., Gu, Y., Zhu, S., Liu, X., Lv, T., & Song, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26733729
Additional file 9 of Overexpression of ESYT3 improves radioimmune responses through activating cGAS-STING pathway in lung adenocarcinoma
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757892

Authors: Chen, D., Barsoumian, H. B., Yang, L., Younes, A. I., Verma, V., Hu, Y., Menon, H., Wasley, M., Masropour, F., Mosaffa, S., Ozgen, T., Klein, K., Cortez, M. A., & Welsh, J. W.
Affiliations: Shandong University (CN)
The University of Texas MD Anderson Cancer Center (US)
Allegheny General Hospital (US)
The University of Texas at Austin (US)
2Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
ORCID: Chen, Dawei
Barsoumian, Hampartsoum B.
Yang, Liangpeng
Younes, Ahmed I.
Verma, Vivek
Hu, Yun
Menon, Hari
Wasley, Mark
Ozgen, Tugce
Welsh, James W.
Venue: Cancer Immunology Research
Publisher: American Association for Cancer Research (AACR)
Published: 2020-07-01
Volume: 8
Issue: 7
Pages: 883-894
ISSN: 2326-6066 (ISSN-L)
2326-6074
DOI: 10.1158/2326-6066.cir-19-0744
PMC: PMC10173258
OpenAlex: W3016731543
Cited by: 107
References: 38
Citations by year: 2026: 10 · 2025: 9 · 2024: 40 · 2023: 14 · 2022: 19 · 2021: 13 · 2020: 2
FWCI: 4.42
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Cancer Immunology Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: NCI NIH (P30 CA016672)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: SHP2, SHP099, PD-L1 blockade, anti-PD-1 resistance, non-small cell lung cancer, radiotherapy, immune checkpoint inhibitors, abscopal effect, tumor-associated macrophages, macrophage polarization, CD8+ T cells, regulatory T cells, lung metastasis, combination immunotherapy
MeSH terms: Antineoplastic Agents, Immunological, Animals, Carcinoma, Non-Small-Cell Lung, Female, Lung Neoplasms, Mice, Inbred C57BL, Piperidines, Pyrimidines, Drug Resistance, Neoplasm, Cell Line, Tumor, Mice, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Mice, 129 Strain, Chemoradiotherapy, B7-H1 Antigen

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

SHP-2 and PD-L1 Inhibition Combined with Radiotherapy Enhances Systemic Antitumor Effects in an Anti–PD-1–Resistant Model of Non–Small Cell Lung Cancer

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks