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 accessPublished version of a preprint
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
Cites
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?
SHP2 inhibitor enhanced the efficacy of α-PD-1 in murine tumor models.
“SHP2 inhibitor enhanced the efficacy of α-PD-1 in murine tumor models [252–254].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [253]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
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 · see citing works
Siegel, R. L., Miller, K. D., & Jemal, A. (2019) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21551 · Cited by 20,160 · see citing works
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 15,314 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 2,101 · see citing works
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 · see citing works
Acquired Resistance to Fractionated Radiotherapy Can Be Overcome by Concurrent PD-L1 Blockade
Dovedi, S. J., Adlard, A. L., Lipowska‐Bhalla, G., McKenna, C., Jones, S., Cheadle, E. J., Stratford, I. J., Poon, E., Morrow, M., Stewart, R. A., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-1258 · Cited by 1,316 · see citing works
Theelen, W. S. M. E., Peulen, H. M. U., Lalezari, F., van der Noort, V., de Vries, J. F., Aerts, J. G. J. V., Dumoulin, D. W., Bahce, I., Niemeijer, A.-L. N., de Langen, A. J., et al. (2019) · JAMA Oncology · doi:10.1001/jamaoncol.2019.1478 · Cited by 1,010 · see citing works
Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases
Chen, Y.-N. P., LaMarche, M. J., Chan, H. M., Fekkes, P., Garcia-Fortanet, J., Acker, M. G., Antonakos, B., Chen, C. H.-T., Chen, Z., Cooke, V. G., et al. (2016) · Nature · doi:10.1038/nature18621 · Cited by 925 · see citing works
SH2-Containing Phosphotyrosine Phosphatase as a Target of Protein-Tyrosine Kinases
Feng, G., Hui, C.-C., & Pawson, T. J. (1993) · Science · doi:10.1126/science.8096088 · Cited by 673 · see citing works
Radiotherapy combination opportunities leveraging immunity for the next oncology practice
Herrera, F. G., Bourhis, J., & Coukos, G. (2016) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21358 · Cited by 511 · see citing works
M1 and M2 Macrophages: The Chicken and the Egg of Immunity
Mills, C. D., & Ley, K. F. (2014) · Journal of Innate Immunity · doi:10.1159/000364945 · Cited by 401 · see citing works
Immunotherapy and stereotactic ablative radiotherapy (ISABR): a curative approach?
Bernstein, M. B., Krishnan, S., Hodge, J. W., & Chang, J. Y. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.30 · Cited by 400 · see citing works
Radiotherapy: Changing the Game in Immunotherapy
Demaria, S., Coleman, C. N., & Formenti, S. C. (2016) · Trends in cancer · doi:10.1016/j.trecan.2016.05.002 · Cited by 367 · see citing works
SHP2 is required for growth of KRAS-mutant non-small-cell lung cancer in vivo
Mainardi, S., Mulero-Sánchez, A., Prahallad, A., Germano, G., Bosma, A., Krimpenfort, P., Lieftink, C., Steinberg, J. D., de Wit, N., Gonçalves-Ribeiro, S., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0023-9 · Cited by 320 · cited 1× · see citing works
“In lung cancer, SHP-2 is required for the growth of KRASmutant and ALK-rearranged NSCLC (13, 14).”
BackgroundTime to abandon single-site irradiation for inducing abscopal effects
Brooks, E. D., & Chang, J. Y. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0119-7 · Cited by 312 · see citing works
Gong, X., Li, X., Jiang, T., Xie, H., Zhu, Z., Zhou, F., & Zhou, C. (2017) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2017.04.014 · Cited by 299 · see citing works
Wang, X., Schoenhals, J. E., Li, A., Valdecanas, D. R., Ye, H., Zang, F., Tang, C. Z., Tang, M., Liu, C., Liu, X., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-3142 · Cited by 261 · see citing works
Self-citationLi, J., Jie, H.-B., Lei, Y. L., Gildener‐Leapman, N., Trivedi, S., Green, T., Kane, L., & Ferris, R. L. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-1215 · Cited by 252 · see citing works
Dardaei, L., Wang, H. Q., Singh, M., Fordjour, P., Shaw, K. X., Yoda, S., Kerr, G., Yu, K., Liang, J., Cao, Y., et al. (2018) · Nature Medicine · doi:10.1038/nm.4497 · Cited by 199 · see citing works
SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade
Zhao, M., Guo, W., Wu, Y., Yang, C., Zhong, L., Deng, G., Zhu, Y., Liu, W., Gu, Y., Lu, Y., et al. (2019) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2018.08.009 · Cited by 190 · see citing works
Vidyarthi, A., Khan, N., Agnihotri, T., Negi, S., Das, D. K., Aqdas, M., Chatterjee, D., Colegio, O. R., Tewari, M. K., & Agrewala, J. N. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01650 · Cited by 157 · see citing works
Role of Radiation Therapy in Modulation of the Tumor Stroma and Microenvironment
Menon, H., Ramapriyan, R., Cushman, T. R., Verma, V., Kim, H. H., Schoenhals, J. E., Atalar, S. C., Selek, U., Chun, S. G., Chang, J. Y., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00193 · Cited by 156 · see citing works
Self-citationAlmatroodi, S. A., McDonald, C. F., Darby, I. A., & Pouniotis, D. S. (2015) · Cancer Microenvironment · doi:10.1007/s12307-015-0174-x · Cited by 144 · see citing works
XIE, C., Liu, C., Wu, B., Yan, L., Ma, T., Xiong, H.-Y., Wang, Q., Li, Z., Ma, C., & Tu, Z. (2016) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2016.2583 · Cited by 100 · see citing works
Schoenhals, J. E., Cushman, T. R., Barsoumian, H. B., Li, A., Cadena, A. P., Niknam, S., Younes, A. I. A., Caetano, M. D. S., Cortez, M. A., & Welsh, J. W. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02170 · Cited by 68 · see citing works
Self-citationGubens, M. A., & Davies, M. J. (2019) · PubMed · doi:10.6004/jnccn.2019.5005 · Cited by 68 · see citing works
Liu, J. J., Li, Y., Chen, W. S., Liang, Y., Wang, G., Zong, M., Kaneko, K., Xu, R., Karin, M., & Feng, G. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.02.014 · Cited by 64 · see citing works
Niknam, S., Barsoumian, H. B., Schoenhals, J. E., Jackson, H. L., Yanamandra, N., Caetano, M. S., Li, A., Younes, A. I. A., Cadena, A. P., Cushman, T. R., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-3279 · Cited by 62 · see citing works
Self-citationXiao, P., Guo, Y. L., Zhang, H., Zhang, X., Cheng, H., Cao, Q., & Ke, Y. (2018) · Oncogene · doi:10.1038/s41388-018-0337-6 · Cited by 54 · see citing works
Shp-2 is critical for ERK and metabolic engagement downstream of IL-15 receptor in NK cells
Niogret, C., Miah, S. M. S., Rota, G., Fonta, N., Wang, H., Held, W., Birchmeier, W., Sexl, V., Yang, W., Vivier, É., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09431-3 · Cited by 46 · see citing works
TLR Agonists That Induce IFN-β Abrogate Resident Macrophage Suppression of T Cells
Hamilton, M. J., Antignano, F., von Rossum, A., Boucher, J., Bennewith, K. L., & Krystal, G. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1002045 · Cited by 22 · see citing works
Chen, D., Song, X., Wang, H., Gao, Z., Meng, W., Chen, S., Ma, Y., Wang, Y., Kong, L., Yu, J., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02916 · Cited by 13 · see citing works
Self-citationChen, D., Song, X., Wang, H., Gao, Z., Meng, W., Chen, S., Ma, Y., Wang, Y., Kong, L., Yu, J., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.649620 · Cited by 6 · see citing works
Self-citation
Flagged first, then by citations
Cited by
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 · see citing works
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 265 · see citing works
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 136 · see citing works
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 · see citing works
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 100 · see citing works
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 99 · see citing works
Self-citationSHP-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 95 · see citing works
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 70 · see citing works
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 · see citing works
Self-citationPakkala, 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 · see citing works
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 59 · see citing works
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 · see citing works
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 56 · see citing works
Self-citationHua, 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 · see citing works
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 53 · see citing works
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 50 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 38 · see citing works
Wang, Q., Bardhan, K., Boussiotis, V. A., & Patsoukis, N. (2021) · Advanced Biology · doi:10.1002/adbi.202100758 · Cited by 39 · see citing works
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 · see citing works
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 37 · see citing works
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 36 · see citing works
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 · see citing works
Tang, X., Qi, C., Zhou, H., & Liu, Y. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.972906 · Cited by 33 · see citing works
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 · see citing works
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 · see citing works
Chen, X., Yang, M., Huang, Y., Tu, J., Cai, Y., & Yuan, X. (2025) · Therapeutic Advances in Medical Oncology · doi:10.1177/17588359251387534 · Cited by 27 · see citing works
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 26 · see citing works
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 24 · see citing works
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 · see citing works
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 25 · see citing works
Mohammad, S. A., Hak, A., Pogu, S. V., & Rengan, A. K. (2023) · Cancer Innovation · doi:10.1002/cai2.53 · Cited by 21 · see citing works
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 · see citing works
Self-citationTumor-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 19 · see citing works
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 17 · see citing works
Local Destruction of Tumors and Systemic Immune Effects
Tranberg, K. ‐. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.708810 · Cited by 16 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Self-citationZhao, 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 · see citing works
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 · see citing works
Liu, X., Zhang, Z., Yuan, J., Yu, J., & Chen, D. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1396719 · Cited by 12 · see citing works
Self-citationMechanism 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 · see citing works
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 11 · see citing works
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 11 · see citing works
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 · see citing works
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 10 · see citing works
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 · see citing works
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 · see citing works
Self-citationVarghese, G. R., Patra, D., Jaikumar, V. S., Rajan, A., Latha, N. R., & Srinivas, P. (2023) · Immunology · doi:10.1111/imm.13673 · Cited by 8 · see citing works
Toral, K., Wuenschel, M. A., & Black, E. P. (2021) · PLoS ONE · doi:10.1371/journal.pone.0256416 · Cited by 8 · see citing works
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 · see citing works
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 7 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 5 · see citing works
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 · see citing works
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 · see citing works
Kiełbowski, K., Bakinowska, E., Becht, R., & Pawlik, A. (2025) · Metabolites · doi:10.3390/metabo15030144 · Cited by 4 · see citing works
Sun, J., Zhou, S., Sun, Y., & Zeng, Y. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1541104 · Cited by 4 · see citing works
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 4 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Self-citationPrecision 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 · see citing works
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 · see citing works
RetractedLv, 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
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
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
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
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757907
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
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757877
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757904
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757889
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
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757910
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
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757901
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757886
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26500319
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
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757880
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757916
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
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757874
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757895
Luo, Z., Li, Y., Xu, B., Yu, T., Luo, M., You, P., Niu, X., & Li, J. (2024) · Figshare · doi:10.6084/m9.figshare.26757919
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
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
- Venue
- Cancer Immunology Research
- Published
- 2020-07-01
- Volume
- 8
- Issue
- 7
- Pages
- 883-894
- ISSN
- 2326-6066 (ISSN-L)
- 2326-6074
- 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
