Neoadjuvant Selicrelumab, an agonist CD40 antibody, induces changes in the tumor microenvironment in patients with resectable pancreatic cancer
Open accessPublished version of a preprint
Abstract
Purpose: CD40 activation is a novel clinical opportunity for cancer immunotherapy. Despite numerous active clinical trials with agonistic CD40 monoclonal antibodies (mAb), biological effects and treatment-related modulation of the tumor microenvironment (TME) remain poorly understood. Patients and Methods: Here, we performed a neoadjuvant clinical trial of agonistic CD40 mAb (selicrelumab) administered intravenously with or without chemotherapy to 16 patients with resectable pancreatic ductal adenocarcinoma (PDAC) before surgery followed by adjuvant chemotherapy and CD40 mAb. Results: The toxicity profile was acceptable, and overall survival was 23.4 months (95% confidence interval, 18.0–28.8 months). Based on a novel multiplexed immunohistochemistry platform, we report evidence that neoadjuvant selicrelumab leads to major differences in the TME compared with resection specimens from treatment-naïve PDAC patients or patients given neoadjuvant chemotherapy/chemoradiotherapy only. For selicrelumab-treated tumors, 82% were T-cell enriched, compared with 37% of untreated tumors (P = 0.004) and 23% of chemotherapy/chemoradiation-treated tumors (P = 0.012). T cells in both the TME and circulation were more active and proliferative after selicrelumab. Tumor fibrosis was reduced, M2-like tumor-associated macrophages were fewer, and intratumoral dendritic cells were more mature. Inflammatory cytokines/sec CXCL10 and CCL22 increased systemically after selicrelumab. Conclusions: This unparalleled examination of CD40 mAb therapeutic mechanisms in patients provides insights for design of subsequent clinical trials targeting CD40 in cancer.
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?
Partly because conventional PDAC drug development has been difficult, the field is shifting from large empirical trials to smaller trials with extensive correlative analyses of response and resistance mechanisms.
“In fact, partly driven by the challenging trajectory of “conventional” drug development in PDAC, there has been an evolving shift from large, empirical trials towards those that are focused on fewer patient numbers, but which feature in-depth correlative studies that provide insights into mechanisms of response and resistance184,292,293.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [184]
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
QuPath: Open source software for digital pathology image analysis
Bankhead, P., Loughrey, M. B., Fernández, J. A., Dombrowski, Y., McArt, D. G., Dunne, P. D., McQuaid, S., Gray, R. T., Murray, L. J., Coleman, H. G., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-17204-5 · Cited by 8,908 · see citing works
Elyada, E., Bolisetty, M., Laise, P., Flynn, W. F., Courtois, E. T., Burkhart, R. A., Teinor, J. A., Belleau, P., Biffi, G., Lucito, M. S., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0094 · Cited by 2,241 · see citing works
Self-citationCD40 Agonists Alter Tumor Stroma and Show Efficacy Against Pancreatic Carcinoma in Mice and Humans
Beatty, G. L., Chiorean, E. G., Fishman, M. P., Saboury, B., Teitelbaum, U. R., Sun, W., Huhn, R. D., Song, W., Li, D., Sharp, L. L., et al. (2011) · Science · doi:10.1126/science.1198443 · Cited by 1,678 · see citing works
Self-citationLi, J., Byrne, K. T., Yan, F., Yamazoe, T., Chen, Z., Baslan, T., Richman, L. P., Lin, J., Sun, Y. H., Rech, A. J., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.06.006 · Cited by 738 · see citing works
Self-citationThe Role of Type 1 Conventional Dendritic Cells in Cancer Immunity
Böttcher, J. P., & Reis e Sousa, C. (2018) · Trends in Cancer · doi:10.1016/j.trecan.2018.09.001 · Cited by 607 · see citing works
Macrophage Polarisation: an Immunohistochemical Approach for Identifying M1 and M2 Macrophages
Barros, M. H., Hauck, F., Dreyer, J., Kempkes, B., & Niedobitek, G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080908 · Cited by 556 · see citing works
Tsujikawa, T., Kumar, S., Borkar, R. N., Azimi, V., Thibault, G., Chang, Y. H., Balter, A. I., Kawashima, R., Choe, G. H., Sauer, D., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.03.037 · Cited by 555 · see citing works
Self-citationMultimodal mapping of the tumor and peripheral blood immune landscape in human pancreatic cancer
Steele, N. G., Carpenter, E. S., Kemp, S. B., Sirihorachai, V. R., The, S., Delrosario, L., Lazarus, J., Amir, E.-A. D., Gunchick, V., Espinoza, C. E., et al. (2020) · Nature Cancer · doi:10.1038/s43018-020-00121-4 · Cited by 546 · see citing works
CD40 agonist antibodies in cancer immunotherapy
Vonderheide, R. H. (2020) · Annual Review of Medicine · doi:10.1146/annurev-med-062518-045435 · Cited by 544 · see citing works
Self-citationVonderheide, R. H., Flaherty, K. T., Khalil, M., Stumacher, M., Bajor, D. L., Hutnick, N. A., Sullivan, P., Mahany, J. J., Gallagher, M., Kramer, A., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.08.3311 · Cited by 513 · see citing works
Self-citationWinograd, R., Byrne, K. T., Evans, R. A., Odorizzi, P. M., Meyer, A. R. L., Bajor, D. L., Clendenin, C., Stanger, B. Z., Furth, E. E., Wherry, E. J., et al. (2015) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0215 · Cited by 459 · see citing works
Self-citationBeatty, G. L., Torigian, D. A., Chiorean, E. G., Saboury, B., Brothers, A., Alavi, A. A., Troxel, A. B., Sun, W., Teitelbaum, U. R., Vonderheide, R. H., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1320 · Cited by 458 · see citing works
Self-citationDendritic Cell Paucity Leads to Dysfunctional Immune Surveillance in Pancreatic Cancer
Hegde, S., Lander, V. E., Herzog, B. H., Zuo, C., Breden, M. A., Knolhoff, B. L., Hogg, G. D., Tang, J. P., Baer, J. M., Mpoy, C., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.02.008 · Cited by 454 · see citing works
Synergy between chemotherapy and immunotherapy in the treatment of established murine solid tumors.
Nowak, A. K., Robinson, B. W. S., & Lake, R. (2003) · PubMed · Cited by 414 · see citing works
O'Hara, M. H., O'Reilly, E. M., Varadhachary, G., Wolff, R. A., Wainberg, Z. A., Ko, A. H., Fisher, G., Rahma, O., Lyman, J. P., Cabanski, C. R., et al. (2021) · The Lancet Oncology · doi:10.1016/s1470-2045(20)30532-5 · Cited by 307 · see citing works
Self-citationThe Immune Revolution: A Case for Priming, Not Checkpoint
Vonderheide, R. H. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.008 · Cited by 294 · see citing works
Self-citationCD40 stimulation obviates innate sensors and drives T cell immunity in cancer
Byrne, K. T., & Vonderheide, R. H. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.058 · Cited by 282 · see citing works
Self-citationLong, K. B., Gladney, W. L., Tooker, G. M., Graham, K. L., Fraietta, J. A., & Beatty, G. L. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-1032 · Cited by 272 · see citing works
Hopkins, A. C., Yarchoan, M., Durham, J. N., Yusko, E. C., Rytlewski, J. A., Robins, H. S., Laheru, D. A., Le, D. T., Lutz, E. R., & Jaffee, E. M. (2018) · JCI Insight · doi:10.1172/jci.insight.122092 · Cited by 233 · cited 1× · see citing works
“We focused on TCR clones identified in the resection sample (we called these “tumor clones”) hypothesizing based on prior studies (24, 25) that this subpopulationmight be enriched for tumor-specific T cells, at least as compared with whole peripheral blood.”
MethodSelf-citationVonderheide, R. H., Burg, J. M., Mick, R., Trosko, J. A., Li, D., Shaik, M. N., Tolcher, A. W., & Hamid, O. (2013) · OncoImmunology · doi:10.4161/onci.23033 · Cited by 202 · see citing works
Self-citationType 1 conventional dendritic cells are systemically dysregulated early in pancreatic carcinogenesis
Lin, J. H., Huffman, A. P., Wattenberg, M. M., Walter, D. M., Carpenter, E. L., Feldser, D. M., Beatty, G. L., Furth, E. E., & Vonderheide, R. H. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20190673 · Cited by 171 · see citing works
Self-citationLiudahl, S. M., Betts, C. B., Sivagnanam, S., Morales-Oyarvide, V., da Silva, A., Yuan, C., Hwang, S., Grossblatt-Wait, A., Leis, K. R., Larson, W., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0841 · Cited by 164 · see citing works
Self-citationTsujikawa, T., Crocenzi, T. S., Durham, J. N., Sugar, E. A., Wu, A. A., Onners, B., Nauroth, J. M., Anders, R. A., Fertig, E. J., Laheru, D. A., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-3978 · Cited by 155 · see citing works
Self-citationSufficiency of CD40 activation and immune checkpoint blockade for T cell priming and tumor immunity
Morrison, A. H., Diamond, M. S., Hay, C. A., Byrne, K. T., & Vonderheide, R. H. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1918971117 · Cited by 149 · see citing works
Self-citationRüter, J., Antonia, S. J., Burris, H. A., Huhn, R. D., & Vonderheide, R. H. (2010) · Cancer Biology & Therapy · doi:10.4161/cbt.10.10.13251 · Cited by 148 · see citing works
Self-citationRadiotherapy and CD40 Activation Separately Augment Immunity to Checkpoint Blockade in Cancer
Rech, A. J., Dada, H., Kotzin, J. J., Henao‐Mejia, J., Minn, A. J., Victor, C. T.-S., & Vonderheide, R. H. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-3821 · Cited by 115 · see citing works
Self-citationA contemporary analysis of survival for resected pancreatic ductal adenocarcinoma
Lewis, R. S., Drebin, J. A., Callery, M. P., Fraker, D. L., Kent, T. S., Gates, J., & Vollmer, C. M. (2012) · HPB · doi:10.1111/j.1477-2574.2012.00571.x · Cited by 112 · see citing works
Banik, G. L., Betts, C. B., Liudahl, S. M., Sivagnanam, S., Kawashima, R., Cotechini, T., Larson, W., Goecks, J., Pai, S. I., Clayburgh, D. R., et al. (2019) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2019.05.039 · Cited by 80 · see citing works
Self-citationGladue, R. P., Paradis, T. J., Cole, S. H., Donovan, C. B., Nelson, R. T., Alpert, R., Gardner, J., Natoli, E. J., Elliott, E. A., Shepard, R. M., et al. (2011) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-011-1014-6 · Cited by 68 · see citing works
Erstad, D. J., Sojoodi, M., Taylor, M. S., Jordan, V. C., Farrar, C. T., Axtell, A. L., Rotile, N. J., Jones, C. M., Graham‐O'Regan, K. A., Ferreira, D. S., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-1359 · Cited by 68 · see citing works
Bajor, D. L., Xu, X., Torigian, D. A., Mick, R., Garcia, L. R., Richman, L. P., Desmarais, C., Nathanson, K. L., Schuchter, L. M., Kalos, M. D., et al. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0154 · Cited by 43 · see citing works
Self-citationRobust Cell Detection and Segmentation for Image Cytometry Reveal Th17 Cell Heterogeneity
Tsujikawa, T., Thibault, G., Azimi, V., Sivagnanam, S., Banik, G. L., Means, C., Kawashima, R., Clayburgh, D. R., Gray, J. W., Coussens, L. M., et al. (2019) · Cytometry Part A · doi:10.1002/cyto.a.23726 · Cited by 21 · see citing works
Self-citationShi, A., Kasumova, G. G., Chien, I., Cintolo-Gonzalez, J., Frederick, D. T., Alpatov, R., Michaud, W. A., Plana, D., Corcoran, R. B., Flaherty, K. T., et al. (2018) · Cancer Research · doi:10.1158/1538-7445.am2018-4282 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Pancreatic cancer: Advances and challenges
Halbrook, C. J., Lyssiotis, C. A., Pasca di Magliano, M., & Maitra, A. (2023) · Cell · doi:10.1016/j.cell.2023.02.014 · Cited by 1,321 · see citing works
Pancreatic Cancer: Pathogenesis, Screening, Diagnosis, and Treatment
Wood, L. D., Canto, M. I., Jaffee, E. M., & Simeone, D. M. (2022) · Gastroenterology · doi:10.1053/j.gastro.2022.03.056 · Cited by 875 · see citing works
Self-citationDendritic cell subsets in cancer immunity and tumor antigen sensing
Prete, A. D., Salvi, V., Soriani, A., Laffranchi, M., Sozio, F., Bosisio, D., & Sozzani, S. (2023) · Cellular and Molecular Immunology · doi:10.1038/s41423-023-00990-6 · Cited by 663 · see citing works
Padrón, L. J., Maurer, D. M., O’Hara, M. H., O’Reilly, E. M., Wolff, R. A., Wainberg, Z. A., Ko, A. H., Fisher, G., Rahma, O., Lyman, J. P., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-01829-9 · Cited by 384 · see citing works
Self-citationImmunotherapy combination approaches: mechanisms, biomarkers and clinical observations
Butterfield, L. H., & Najjar, Y. G. (2023) · Nature reviews. Immunology · doi:10.1038/s41577-023-00973-8 · Cited by 355 · see citing works
Dendritic cells as shepherds of T cell immunity in cancer
Pittet, M. J., Pilato, M. D., Garris, C., & Mempel, T. R. (2023) · Immunity · doi:10.1016/j.immuni.2023.08.014 · Cited by 326 · see citing works
Immunologic Strategies in Pancreatic Cancer: Making Cold Tumors Hot
Ullman, N. A., Burchard, P. R., Dunne, R. F., & Linehan, D. C. (2022) · Journal of Clinical Oncology · doi:10.1200/jco.21.02616 · Cited by 304 · see citing works
Cancer therapy with antibodies
Paul, S., Konig, M. F., Pardoll, D. M., Bettegowda, C., Papadopoulos, N., Wright, K. M., Gabelli, S. B., Ho, M., van Elsas, A., & Zhou, S. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00690-x · Cited by 271 · see citing works
Current and future immunotherapeutic approaches in pancreatic cancer treatment
Farhangnia, P., Khorramdelazad, H., Nickho, H., & Delbandi, A. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01561-6 · Cited by 247 · see citing works
Liudahl, S. M., Betts, C. B., Sivagnanam, S., Morales-Oyarvide, V., da Silva, A., Yuan, C., Hwang, S., Grossblatt-Wait, A., Leis, K. R., Larson, W., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0841 · Cited by 164 · see citing works
Self-citationLu, C., Liu, Y., Ali, N. M., Zhang, B., & Cui, X. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1039260 · Cited by 148 · see citing works
Immune Checkpoint Therapies and Atherosclerosis: Mechanisms and Clinical Implications
Vuong, J. T., Stein-Merlob, A. F., Nayeri, A., Sallam, T., Neilan, T. G., & Yang, E. H. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.11.048 · Cited by 113 · see citing works
Tumor-associated macrophages in multiple myeloma: advances in biology and therapy
Sun, J., Park, C., Guenthner, N., Gurley, S., Zhang, L.-N., Lubben, B., Adebayo, O., Bash, H., Chen, Y., Maksimos, M., et al. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-003975 · Cited by 85 · see citing works
Atherosclerosis With Immune Checkpoint Inhibitor Therapy
Abreu, G. A. S., Zanni, M. V., & Neilan, T. G. (2022) · JACC CardioOncology · doi:10.1016/j.jaccao.2022.11.011 · Cited by 103 · see citing works
Heumann, T. R., Judkins, C., Li, K., Lim, S. J., Hoare, J., Parkinson, R. M., Cao, H., Zhang, T., Gai, J., Celiker, B., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39196-9 · Cited by 98 · see citing works
Self-citationConsensus, debate, and prospective on pancreatic cancer treatments
Wang, J., Yang, J., Narang, A. K., He, J., Wolfgang, C. L., Li, K., & Zheng, L. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01613-x · Cited by 99 · see citing works
Targeting lipid metabolism of macrophages: A new strategy for tumor therapy
Shao, N., Qiu, H., Liu, J., Xiao, D., Zhao, J., Chen, C., Wan, J., Guo, M., Liang, G., Zhao, X., et al. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.02.009 · Cited by 94 · see citing works
Targeting the TNF and TNFR superfamilies in autoimmune disease and cancer
Croft, M., Salek‐Ardakani, S., & Ware, C. F. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01053-9 · Cited by 98 · see citing works
Gautam, S. K., Batra, S. K., & Jain, M. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01813-y · Cited by 88 · see citing works
Macrophages and fibroblasts as regulators of the immune response in pancreatic cancer
Shakiba, M., & Tuveson, D. A. (2025) · Nature Immunology · doi:10.1038/s41590-025-02134-6 · Cited by 75 · see citing works
Luo, W., Wen, T., & Qu, X. (2024) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-023-02935-3 · Cited by 68 · see citing works
Innate immune cells in tumor microenvironment: A new frontier in cancer immunotherapy
Li, C., Yu, X., Han, X., Chen, L., Wang, Z., Shao, S., Shao, F., Wang, H., Ma, S., & Liu, J. (2024) · iScience · doi:10.1016/j.isci.2024.110750 · Cited by 58 · see citing works
Harnessing the potential of CD40 agonism in cancer therapy
Zhou, Y., Richmond, A. J., & Yan, C. W. (2023) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2023.11.002 · Cited by 55 · see citing works
Strategies to overcome DC dysregulation in the tumor microenvironment
Mestrallet, G., Sone, K., & Bhardwaj, N. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.980709 · Cited by 54 · see citing works
Clinical immunotherapy in pancreatic cancer
Ye, X., Yu, Y., Zheng, X., & Ma, H. (2024) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-024-03632-6 · Cited by 54 · see citing works
Charting roadmaps towards novel and safe synergistic immunotherapy combinations
Sanmamed, M. F., Berraondo, P., Rodriguez-Ruiz, M. E., & Melero, I. (2022) · Nature Cancer · doi:10.1038/s43018-022-00401-1 · Cited by 50 · see citing works
Immunocytes in the tumor microenvironment: recent updates and interconnections
Yu, J., Fu, L., Wu, R., Che, L., Liu, G., Ran, Q., Xia, Z., Liang, X., & Zhao, G. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1517959 · Cited by 52 · see citing works
Group Young Researchers in Inflammatory Carcinogenesis, Wandmacher, A. M., Mehdorn, A., & Sebens, S. (2021) · Cancers · doi:10.3390/cancers13194932 · Cited by 44 · see citing works
Narayanan, J. S. S., Hayashi, T., Erdem, S., McArdle, S., Tiriac, H., Ray, P., Pu, M., Mikulski, Z., Miller, A. M., Messer, K. S., et al. (2023) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-006133 · Cited by 45 · see citing works
Breaking the stromal barrier in pancreatic cancer: Advances and challenges
Chakkera, M., Foote, J. B., Farran, B., & Nagaraju, G. P. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.189065 · Cited by 44 · see citing works
Liu, H., Gonzalez, D. D., Viswanath, D. I., Pol, R. V., Saunders, S. Z., Trani, N. D., Xu, Y., Zheng, J., Chen, S., Chua, C. Y. X., et al. (2023) · Advanced Science · doi:10.1002/advs.202206873 · Cited by 42 · see citing works
Croft, W. D., Pearce, H., Margielewska‐Davies, S., Lim, L., Nicol, S. M., Zayou, F., Blakeway, D., Marcon, F., Powell-Brett, S. F., Mahon, B. S., et al. (2023) · eLife · doi:10.7554/elife.86125 · Cited by 43 · see citing works
Facts and Hopes of CD40 Agonists in Cancer Immunotherapy
McVey, J. C., & Beatty, G. L. (2025) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-24-1660 · Cited by 44 · see citing works
Clinical Strategies Targeting the Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma
Skorupan, N., Domínguez, M. P., Ricci, S. L., & Alewine, C. (2022) · Cancers · doi:10.3390/cancers14174209 · Cited by 32 · see citing works
Innate immune cells: Key players of orchestra in modulating tumor microenvironment (TME)
Sadeghi, M., Dehnavi, S., Sharifat, M., Amiri, A. M., & Khodadadi, A. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e27480 · Cited by 34 · see citing works
Neoadjuvant therapy alters the immune microenvironment in pancreatic cancer
Zhang, H., Ye, L., Yu, X., Jin, K., & Wu, W. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.956984 · Cited by 34 · see citing works
Multiplexed Imaging Mass Cytometry Analysis Characterizes the Vascular Niche in Pancreatic Cancer
Sussman, J., Kim, N., Kemp, S. B., Traum, D., Katsuda, T., Kahn, B., Xu, J., Kim, I., Eskandarian, C., Delman, D., et al. (2024) · Cancer Research · doi:10.1158/0008-5472.can-23-2352 · Cited by 32 · see citing works
Blise, K. E., Sivagnanam, S., Betts, C. B., Betre, K., Kirchberger, N. C., Tate, B. J., Furth, E. E., Costa, A. D., Nowak, J. A., Wolpin, B. M., et al. (2024) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-23-0873 · Cited by 30 · see citing works
Self-citationNext-generation CD40 agonists for cancer immunotherapy
Andersson, H., Nyesiga, B., Hermodsson, T., Smith, K. E., Hägerbrand, K., Lindstedt, M., & Ellmark, P. (2024) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2024.2357714 · Cited by 30 · see citing works
Liu, R., Li, J., Liu, L., Wang, W., & Jia, J. (2024) · Cancer Pathogenesis and Therapy · doi:10.1016/j.cpt.2024.07.004 · Cited by 31 · see citing works
A potential novel cancer immunotherapy: Agonistic anti-CD40 antibodies
Jian, C.-Z., Li, L., Hsu, C., Chen, Y.-H., Hsu, C., Tan, C., & Ou, D. (2024) · Drug Discovery Today · doi:10.1016/j.drudis.2024.103893 · Cited by 28 · see citing works
Li, Q., He, J., Li, S., Tian, C., Yang, J., Yuan, H., Lu, Y. H., Fagone, P., Nicoletti, F., & Xiang, M. (2022) · Clinical Immunology · doi:10.1016/j.clim.2022.109217 · Cited by 28 · see citing works
Advances in Immunotherapeutics in Pancreatic Ductal Adenocarcinoma
Chouari, T. A. M., Costa, F. L., Merali, N., Jessel, M.-D., Sivakumar, S., Annels, N. E., & Frampton, A. E. (2023) · Cancers · doi:10.3390/cancers15174265 · Cited by 30 · see citing works
Olaoba, O. T., Yang, M. J., Adelusi, T. I., Maidens, T., Kimchi, E. T., Staveley-O’Carroll, K. F., & Li, G. (2024) · Cancers · doi:10.3390/cancers16081470 · Cited by 27 · see citing works
Hou, W., Yang, B., & Zhu, H. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14102033 · Cited by 26 · see citing works
Dendritic Cells: The Long and Evolving Road towards Successful Targetability in Cancer
Marmonti, E., Oliva, J., & Haymaker, C. (2022) · Cells · doi:10.3390/cells11193028 · Cited by 27 · see citing works
Wang, Z., Zhong, H., Liang, X.-H., & Ni, S.-L. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1024921 · Cited by 32 · see citing works
The Immune Landscape of Pheochromocytoma and Paraganglioma: Current Advances and Perspectives
Uher, O., Vanova, K. H., Taïeb, D., Calsina, B., Robledo, M., Clifton-Bligh, R. J., & Pacák, K. (2024) · Endocrine Reviews · doi:10.1210/endrev/bnae005 · Cited by 29 · see citing works
Frankish, J., Mukherjee, D., Romano, E., Frey, K., Schröder, M., Heinonen, K., Merz, C., Müller, M. R., Gieffers, C., Hill, O., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1160116 · Cited by 25 · see citing works
Oncolytic adenovirus as pancreatic cancer-targeted therapy: Where do we go from here?
Yoon, A. R., Hong, J., Jung, B., Ahn, H. M., Zhang, S., & Yun, C. (2023) · Cancer Letters · doi:10.1016/j.canlet.2023.216456 · Cited by 24 · see citing works
Cai, R., Zhu, H., Liu, Y. L., Sha, H., Peng, W., Yin, R. L., Zhou, G., & Fang, Y. (2023) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-023-04919-4 · Cited by 23 · see citing works
Karamitopoulou, E., Wenning, A. S., Acharjee, A., Aeschbacher, P., Marinoni, I., Zlobec, I., Gloor, B., & Perren, A. A. (2024) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-24-0368 · Cited by 23 · see citing works
Precision Targeting Strategies in Pancreatic Cancer: The Role of Tumor Microenvironment
Vitorakis, N., Gargalionis, A. N., Papavassiliou, K. A., Adamopoulos, C., & Papavassiliou, A. G. (2024) · Cancers · doi:10.3390/cancers16162876 · Cited by 22 · see citing works
Neoadjuvant Immunotherapy for Localized Pancreatic Cancer: Challenges and Early Results
Chick, R. C., Gunderson, A. J., Rahman, S., & Cloyd, J. M. (2023) · Cancers · doi:10.3390/cancers15153967 · Cited by 22 · see citing works
Li, J., Wei, T., Ma, K., Zhang, J., Lü, J., Zhao, J., Huang, J., Zeng, T., Xie, Y., Liang, Y., et al. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216607 · Cited by 21 · see citing works
Macrophage heterogeneity and its interactions with stromal cells in tumour microenvironment
Cao, L., Meng, X., Zhang, Z., Liu, Z., & He, Y. (2024) · Cell & Bioscience · doi:10.1186/s13578-024-01201-z · Cited by 20 · see citing works
The cross-talk between macrophages and tumor cells as a target for cancer treatment
Aizaz, M., Khan, A. U., Khan, F., Khan, M., Saleh, E. A. M., Nisar, M., & Baran, N. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1259034 · Cited by 20 · see citing works
Challenges and Opportunities in Targeting the Complex Pancreatic Tumor Microenvironment
Finan, J. M., Guo, Y., Goodyear, S. M., & Brody, J. R. (2024) · JCO oncology advances. · doi:10.1200/oa-24-00050 · Cited by 20 · see citing works
Lu, C., Liu, Y., Miao, L., Kong, X., Li, H., Chen, H., Zhao, X., Zhang, B., & Cui, X. (2023) · International Journal of Oncology · doi:10.3892/ijo.2023.5599 · Cited by 19 · see citing works
Kuznetsova, A. B., Kolesova, E. P., Parodi, A., Zamyatnin, A. A., & Egorova, V. S. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16050636 · Cited by 19 · see citing works
Dendritic cell immunotherapy advances for solid tumors: Vaccination and modulation
Clayton, G., Toffoli, E. C., de Gruijl, T. D., & van Kooyk, Y. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102412 · Cited by 19 · see citing works
Silva, A. J. D., de Moura, I. A., da Gama, M. A. T. M., Leal, L. R. S., de Pinho, S. S., Espinoza, B. C. F., dos Santos, D. L., Santos, V. E. P., de Sena, M. G. A. M., Invenção, M. D. C. V., et al. (2023) · Vaccines · doi:10.3390/vaccines11081354 · Cited by 19 · see citing works
Advances in immunotherapy and targeted therapy for pancreatic cancer
Zhou, X., Wang, X., Yang, S., & Huang, Z. (2024) · Oncology and Translational Medicine · doi:10.1097/ot9.0000000000000074 · Cited by 19 · see citing works
Toulmonde, M., Guégan, J., Ceruso, M. S., Valentin, T., Bahleda, R., Peyraud, F., Rey, C., Kind, M., Cantarel, C., Bellera, C. A., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02278-9 · Cited by 19 · see citing works
Lin, H.-J. L., Liu, Y., Caroland, K. P., & Lin, J. (2023) · Cancers · doi:10.3390/cancers15133507 · Cited by 19 · see citing works
Combination immunotherapy for pancreatic cancer: challenges and future considerations
Gössling, G. C. D. L., Zhen, D. B., Pillarisetty, V. G., & Chiorean, E. G. (2022) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2022.2120471 · Cited by 18 · see citing works
Self-citationRole of M2 macrophage-derived exosomes in cancer drug resistance via noncoding RNAs
Hu, X., Li, Y., Wang, X., & Xue, X. (2025) · Discover Oncology · doi:10.1007/s12672-025-02195-x · Cited by 17 · see citing works
Updates in Immunotherapy for Pancreatic Cancer
Chick, R. C., & Pawlik, T. M. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13216419 · Cited by 16 · see citing works
Norgard, R. J., Budhani, P., O’Brien, S. A., Xia, Y., Egan, J. N., Flynn, B., Tagore, J. R., Seco, J., Peet, G. W., Mikucka, A., et al. (2024) · Cancer Research Communications · doi:10.1158/2767-9764.crc-24-0172 · Cited by 16 · see citing works
Agostini, A., Orlacchio, A., Carbone, C., & Guerriero, I. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.876291 · Cited by 14 · see citing works
A Paradigm Shifts: Neoadjuvant Therapy for Clearly Resectable Pancreatic Cancer
de Geus, S. W. L., & Sachs, T. E. (2023) · Annals of Surgical Oncology · doi:10.1245/s10434-023-13281-1 · Cited by 15 · see citing works
Zhou, P., Zhang, W., Liao, Y., Zhai, Z., Lu, S., Jiang, S., Hu, W., & Gong, W. (2025) · International Journal of Surgery · doi:10.1097/js9.0000000000002573 · Cited by 15 · see citing works
Next‐Generation Immune Checkpoints and Tumor Microenvironment Modulation in Cancer Immunotherapy
Bautista, J., Echeverría, C. E., Maldonado-Noboa, I., Adatty-Molina, J., Urresta, S. S., Coral-Riofrio, E. C., Araujo‐Abad, S., Kyriakidis, N. C., & López-Cortés, A. (2026) · Journal of Immunology Research · doi:10.1155/jimr/7864229 · Cited by 15 · see citing works
The Next Frontier in Pancreatic Cancer: Targeting the Tumor Immune Milieu and Molecular Pathways
Yin, C., Alqahtani, A. J., & Noel, M. S. (2022) · Cancers · doi:10.3390/cancers14112619 · Cited by 14 · see citing works
Wang, Y., Yue, B., Ni, H., Chen, J., Shi, R., Wang, Z., Dai, X., & Sheng, M. (2026) · Translational Oncology · doi:10.1016/j.tranon.2026.102682 · Cited by 13 · see citing works
Iron-Dependent Cell Death: A New Treatment Approach against Pancreatic Ductal Adenocarcinoma
Lopez-Blazquez, C., Lacalle-González, C., Sanz-Criado, L., Otieno, M. O., García‐Foncillas, J., & Martínez‐Useros, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914979 · Cited by 15 · see citing works
Clinical Evaluation of the Pancreatic Cancer Microenvironment: Opportunities and Challenges
Szczepanski, J. M., Rudolf, M. A., & Shi, J. (2024) · Cancers · doi:10.3390/cancers16040794 · Cited by 13 · see citing works
Lu, K., Wang, W., Liu, Y., Xie, C., Liu, J., & Xing, L. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1413494 · Cited by 13 · see citing works
Ma, H., Chen, X., Mo, S., Mao, X., Chen, J., Liu, Y., Lu, Z., Yu, S., & Chen, J. (2023) · Theranostics · doi:10.7150/thno.86547 · Cited by 13 · see citing works
Kucukcelebi, S., Land, F. R. V. ‘., van der Burg, S. H., Eskens, F. A. L. M., Homs, M. Y. V., Willemsen, M., Schoonhoven, A. O.-V., Rozendaal, N. E. M., Fellah, A., Vadgama, D., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-66092-1 · Cited by 12 · see citing works
Aghamajidi, A., Farhangnia, P., Pashangzadeh, S., Damavandi, A. R., & Jafari, R. (2022) · Cancer Cell International · doi:10.1186/s12935-022-02727-3 · Cited by 12 · see citing works
Guo, S., & Wang, Z. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1349308 · Cited by 12 · see citing works
Zhao, Y., Qin, C., Chen, L., Li, Z., Zhao, B., Li, T., Zhang, X., & Wang, W. (2024) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2024.189183 · Cited by 13 · see citing works
Pratt, H. G., Ma, L., Dziadowicz, S. A., Ott, S., Whalley, T., Szomolay, B., Eubank, T. D., Hu, G., & Boone, B. A. (2024) · Clinical and Translational Medicine · doi:10.1002/ctm2.1595 · Cited by 10 · see citing works
Intratumoral NKT cell accumulation promotes antitumor immunity in pancreatic cancer
Li, J., Moresco, P., & Fearon, D. T. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2403917121 · Cited by 9 · see citing works
From silent partners to potential therapeutic targets: macrophages in colorectal cancer
Khizar, H., Ali, K., & Wang, J. (2025) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-025-03965-w · Cited by 11 · see citing works
Remodeling the Tumor Myeloid Landscape to Enhance Antitumor Antibody Immunotherapies
Hussain, K., Cragg, M. S., & Beers, S. A. (2021) · Cancers · doi:10.3390/cancers13194904 · Cited by 11 · see citing works
Badillo, O., Helfridsson, L., Niemi, J. V. L., & Hellström, M. (2024) · Upsala Journal of Medical Sciences · doi:10.48101/ujms.v129.10627 · Cited by 11 · see citing works
Targeting tumor-associated macrophages to reverse antitumor drug resistance
Li, S., Sheng, J., Zhang, D., & Qin, H. (2024) · Aging · doi:10.18632/aging.205858 · Cited by 11 · see citing works
Al-Khinji, A., Al-Korbi, N., Al-Kuwari, S., Al-Hor, A., & Malouche, D. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1569884 · Cited by 10 · see citing works
Miliotou, Α. N., Georgiou‐Siafis, S. K., Ntenti, C., Pappas, I. S., & Papadopoulou, L. C. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45110576 · Cited by 11 · see citing works
Panoramic tumor microenvironment in pancreatic ductal adenocarcinoma
Li, X., Hou, W., Xiao, C., Yang, H., Zhao, C., & Cao, D. (2024) · Cellular Oncology · doi:10.1007/s13402-024-00970-6 · Cited by 10 · see citing works
Heirene, L., Byrne, H. M., Sepp, A., Gaffney, E. A., & Yates, J. W. T. (2025) · Journal of The Royal Society Interface · doi:10.1098/rsif.2024.0710 · Cited by 10 · see citing works
Soto, M., Filbert, E. L., Yang, H. L., Starzinski, S., Starzinski, A., Gin, M., Chen, B. K., Le, P. L., Li, T., Bol, B., et al. (2024) · Cancer Research Communications · doi:10.1158/2767-9764.crc-23-0550 · Cited by 10 · see citing works
Sarfraz, Z., Sarfraz, A., Farooq, M. D., Khalid, M., Cheema, K., Javad, F., Khan, T., Pervaiz, Z., Sarfraz, M., Jaan, A., et al. (2024) · Journal of Gastrointestinal Cancer · doi:10.1007/s12029-024-01078-8 · Cited by 10 · see citing works
Zhu, T., Wu, X., Liao, Y., Yan, Y., Yu, M., Wang, L., & Xia, Q. (2023) · Clinical Cancer Bulletin · doi:10.1007/s44272-023-00005-5 · Cited by 8 · see citing works
Li, J., Ye, Z., Hu, X., Hou, S., & Hang, Q. (2022) · Cancers · doi:10.3390/cancers14246187 · Cited by 9 · see citing works
Palma, A. M., Vudatha, V., Peixoto, M. L., & Madan, E. (2023) · Advances in cancer research · doi:10.1016/bs.acr.2023.02.005 · Cited by 9 · see citing works
Zhou, Q., Chen, D., Zhang, J., Xiang, J.-F., Zhang, T., Wang, H., & Zhang, Y. (2022) · Journal of Pancreatology · doi:10.1097/jp9.0000000000000109 · Cited by 9 · see citing works
- Authors
- Byrne, K. T., Betts, C. B., Mick, R., Sivagnanam, S., Bajor, D. L., Laheru, D. A., Chiorean, E. G., O'Hara, M. H., Liudahl, S. M., Newcomb, C., Alanio, C., Ferreira, A. P., Park, B. S., Ohtani, T., Huffman, A. P., Väyrynen, S. A., Dias Costa, A., Kaiser, J. C., Lacroix, A. M., Redlinger, C., Stern, M., Nowak, J. A., Wherry, E. J., Cheever, M. A., Wolpin, B. M., Furth, E. E., Jaffee, E. M., Coussens, L. M., & Vonderheide, R. H.
- Affiliations
- University of Pennsylvania (US)
- Portland State University (US)
- Oregon Health & Science University (US)
- Case Comprehensive Cancer Center (US)
- Johns Hopkins University (US)
- University of Washington (US)
- 1Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
- Harvard University (US)
- 10Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
- Fred Hutch Cancer Center (US)
- F. Hoffmann-La Roche AG (CH)
- Brigham and Women's Hospital (US)
- Corresponding author
- Vonderheide, Robert H.
- ORCID
- Byrne, Katelyn T.
- Betts, Courtney B.
- Mick, Rosemarie
- Sivagnanam, Shamilene
- Bajor, David L.
- Laheru, Daniel A.
- Chiorean, E. Gabriela
- Liudahl, Shannon M.
- Newcomb, Craig
- Alanio, Cécile
- Ferreira, Ana P.
- Park, Byung S.
- Ohtani, Takuya
- Väyrynen, Sara A.
- Kaiser, Judith C.
- Lacroix, Andreanne M.
- Nowak, Jonathan A.
- Wherry, E. John
- Cheever, Martin A.
- Wolpin, Brian M.
- Furth, Emma E.
- Jaffee, Elizabeth M.
- Coussens, Lisa M.
- Vonderheide, Robert H.
- Venue
- Clinical Cancer Research
- Published
- 2021-06-10
- Volume
- 27
- Issue
- 16
- Pages
- 4574-4586
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC8667686
- OpenAlex
- W3171434019
- Cited by
- 199
- References
- 33
- Citations by year
- 2026: 37 · 2025: 42 · 2024: 48 · 2023: 41 · 2022: 28 · 2021: 3
- FWCI
- 10.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Clinical Cancer Research (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- SU2C-Lustgarten Foundation (SU2C-AACR-DT14-14)
- Pancreatic Cancer Action Network (Research Acceleration Network)
- Lustgarten Foundation (NA)
- National Cancer Institute (P30CA016520, R01CA229803, R01CA169123, U01CA224012, U2CCA233280, R01CA223150, R01CA226909, R21HD099367, UM1CA154967)
- Parker Institute for Cancer Immunotherapy (NA)
- Brenden-Colson Center for Pancreatic Care (NA)
- Hale Center for Pancreatic Cancer Research (NA)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- pancreatic ductal adenocarcinoma, neoadjuvant therapy, tumor microenvironment, T cell infiltration, tumor-associated macrophages, M2 macrophages, dendritic cell maturation, tumor fibrosis, cancer immunotherapy, overall survival
- MeSH terms
- Adult, Aged, Antibodies, Monoclonal, Female, Humans, Male, Middle Aged, Pancreatic Neoplasms, CD40 Antigens, Neoadjuvant Therapy, Tumor Microenvironment, Antibodies, Monoclonal, Humanized
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
