Tumor microenvironment and therapeutic response

Hallmarks of Cancer: The Next Generation

Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590

Microenvironmental regulation of tumor progression and metastasis

Quail, D. F., & Joyce, J. A. (2013) · Nature Medicine · doi:10.1038/nm.3394 · Cited by 7,994

Macrophage Diversity Enhances Tumor Progression and Metastasis

Qian, B., & Pollard, J. W. (2010) · Cell · doi:10.1016/j.cell.2010.03.014 · Cited by 5,338

Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment

Hanahan, D., & Coussens, L. M. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.022 · Cited by 4,632

Fibroblasts in cancer

Kalluri, R., & Zeisberg, M. (2006) · Nature Reviews Cancer · doi:10.1038/nrc1877 · Cited by 4,538

Stromal Fibroblasts Present in Invasive Human Breast Carcinomas Promote Tumor Growth and Angiogenesis through Elevated SDF-1/CXCL12 Secretion

Orimo, A., Gupta, P. B., Sgroi, D. C., Arenzana-Seisdedos, F., Delaunay, T., Naeem, R., Carey, V. J., Richardson, A. L., & Weinberg, R. A. (2005) · Cell · doi:10.1016/j.cell.2005.02.034 · Cited by 3,759

Coordinated regulation of myeloid cells by tumours

Gabrilovich, D. I., Ostrand-Rosenberg, S., & Bronte, V. (2012) · Nature Reviews Immunology · doi:10.1038/nri3175 · Cited by 3,544

Immunogenic Cell Death in Cancer Therapy

Kroemer, G., Galluzzi, L., Kepp, O., & Zitvogel, L. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-100008 · Cited by 3,303

CSF-1R inhibition alters macrophage polarization and blocks glioma progression

Pyonteck, S. M., Akkari, L., Schuhmacher, A. J., Bowman, R. L., Sevenich, L., Quail, D. F., Olson, O. C., Quick, M. L., Huse, J. T., Teijeiro, V., et al. (2013) · Nature Medicine · doi:10.1038/nm.3337 · Cited by 2,463

Macrophage plasticity and polarization in tissue repair and remodelling

Mantovani, A., Biswas, S. K., Galdiero, M. R., Sica, A., & Locati, M. (2013) · The Journal of Pathology · doi:10.1002/path.4133 · Cited by 2,384

Putting tumours in context

Bissell, M. J., & Radisky, D. (2001) · Nature Reviews Cancer · doi:10.1038/35094059 · Cited by 2,180

Drug Resistance and the Solid Tumor Microenvironment

Tredan, O., Galmarini, C. M., Patel, K., & Tannock, I. F. (2007) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djm135 · Cited by 2,116

Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion

Straussman, R., Morikawa, T., Shee, K., Barzily-Rokni, M., Qian, Z. R., Du, J., Davis, A., Mongare, M. M., Gould, J., Frederick, D. T., et al. (2012) · Nature · doi:10.1038/nature11183 · Cited by 1,771

Leukocyte Complexity Predicts Breast Cancer Survival and Functionally Regulates Response to Chemotherapy

DeNardo, D. G., Brennan, D. J., Rexhepaj, E., Ruffell, B., Shiao, S. L., Madden, S. F., Gallagher, W. M., Wadhwani, N., Keil, S. D., Junaid, S. A., et al. (2011) · Cancer Discovery · doi:10.1158/2159-8274.cd-10-0028 · Cited by 1,715

CD40 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 1,706

Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy.

Ries, C. H., Cannarile, M. A., Hoves, S., Benz, J., Wartha, K., Runza, V., Rey-Giraud, F., Pradel, L. P., Feuerhake, F., Klaman, I., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.05.016 · Cited by 1,384

Macrophage polarization in tumour progression

Sica, A., Larghi, P., Mancino, A., Rubino, L., Porta, C., Totaro, M. G., Rimoldi, M., Biswas, S. K., Allavena, P., & Mantovani, A. (2008) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2008.03.004 · Cited by 1,241

Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor

Kim, S., Turnbull, J. E., & Guimond, S. E. (2011) · Journal of Endocrinology · doi:10.1530/joe-10-0377 · Cited by 1,206

Role of extracellular matrix assembly in interstitial transport in solid tumors.

Netti, P. A., Berk, D. A., Swartz, M. A., Grodzinsky, A. J., & Jain, R. K. (2000) · PubMed · Cited by 1,165

History of myeloid-derived suppressor cells

Talmadge, J. E., & Gabrilovich, D. I. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3581 · Cited by 1,148

Immunological hallmarks of stromal cells in the tumour microenvironment

Turley, S. J., Cremasco, V., & Astarita, J. L. (2015) · Nature Reviews Immunology · doi:10.1038/nri3902 · Cited by 1,140

A CXCL1 Paracrine Network Links Cancer Chemoresistance and Metastasis

Acharyya, S., Oskarsson, T., Vanharanta, S., Malladi, S., Kim, J., Morris, P. G., Manova-Todorova, K., Leversha, M., Hogg, N., Seshan, V. E., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.042 · Cited by 1,085

Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial

Stupp, R., Hegi, M. E., Gorlia, T., Erridge, S. C., Perry, J., Hong, Y.-K., Aldape, K. D., Lhermitte, B., Pietsch, T., Grujicic, D., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70379-1 · Cited by 1,052

Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells

Ruffell, B., Chang-Strachan, D., Chan, V., Rosenbusch, A., Ho, C. M. T., Pryer, N., Daniel, D., Hwang, E. S., Rugo, H. S., & Coussens, L. M. (2014) · Cancer Cell · doi:10.1016/j.ccell.2014.09.006 · Cited by 1,008

Tumor Induction of VEGF Promoter Activity in Stromal Cells

Fukumura, D., Xavier, R., Sugiura, T., Chen, Y., Park, E.-C., Lu, N., Selig, M., Nielsen, G., Taksir, T., Jain, R. K., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81731-6 · Cited by 996

Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer

Bracci, L., Schiavoni, G., Sistigu, A., & Belardelli, F. (2013) · Cell Death and Differentiation · doi:10.1038/cdd.2013.67 · Cited by 951

Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer

Bayne, L. J., Beatty, G. L., Jhala, N., Clark, C. E., Rhim, A. D., Stanger, B. Z., & Vonderheide, R. H. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.04.025 · Cited by 947

Environment-mediated drug resistance: A major contributor to minimal residual disease

Meads, M. B., Gatenby, R. A., & Dalton, W. S. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2714 · Cited by 892

Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells

Shojaei, F., Wu, X., Malik, A. K., Zhong, C., Baldwin, M. E., Schanz, S., Fuh, G., Gerber, H.-P., & Ferrara, N. (2007) · Nature Biotechnology · doi:10.1038/nbt1323 · Cited by 849

Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth

Bruchard, M., Mignot, G., Dérangère, V., Chalmin, F., Chevriaux, A., Végran, F., Boireau, W., Simon, B., Ryffel, B., Connat, J., et al. (2012) · Nature Medicine · doi:10.1038/nm.2999 · Cited by 797

Microenvironmental regulation of therapeutic response in cancer

Klemm, F., & Joyce, J. A. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.11.006 · Cited by 795

“Re-educating” tumor-associated macrophages by targeting NF-κB

Hagemann, T., Lawrence, T., McNeish, I., Charles, K. A., Kulbe, H., Thompson, R. G., Robinson, S. C., & Balkwill, F. R. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20080108 · Cited by 792

Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function

Serafini, P., Meckel, K. F., Kelso, M., Noonan, K. A., Califano, J. A., Koch, W. M., Dolcetti, L., Bronte, V., & Borrello, I. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20061104 · Cited by 780

Disruption of CXCR2-Mediated MDSC Tumor Trafficking Enhances Anti-PD1 Efficacy

Highfill, S. L., Cui, Y., Giles, A. J., Smith, J. P., Zhang, H., Morse, E., Kaplan, R. N., & Mackall, C. L. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007974 · Cited by 767

Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell–derived factor-1

Burger, J. A., Tsukada, N., Burger, M., Zvaifler, N. J., Dell’Aquila, M. L., & Kipps, T. J. (2000) · Blood · doi:10.1182/blood.v96.8.2655 · Cited by 752

Macrophages and cancer: from mechanisms to therapeutic implications

Ostuni, R., Kratochvill, F., Murray, P. J., & Natoli, G. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.02.004 · Cited by 709

Bv8 regulates myeloid-cell-dependent tumour angiogenesis

Shojaei, F., Wu, X., Zhong, C., Yu, L., Liang, X., Yao, J. J., Blanchard, D., Bais, C., Peale, F. V., Jr., van Bruggen, N., et al. (2007) · Nature · doi:10.1038/nature06348 · Cited by 652

The interaction of anticancer therapies with tumor-associated macrophages

Mantovani, A., & Allavena, P. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20150295 · Cited by 634

Targeting tumor‐associated fibroblasts improves cancer chemotherapy by increasing intratumoral drug uptake

Loeffler, M. (2006) · Journal of Clinical Investigation · doi:10.1172/jci26532 · Cited by 633

Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia

Matsunaga, T., Takemoto, N., Sato, T., Takimoto, R., Tanaka, I., Fujimi, A., Akiyama, T., Kuroda, H., Kawano, Y., Kobune, M., et al. (2003) · Nature Medicine · doi:10.1038/nm909 · Cited by 574

Vascular endothelial growth factor and interleukin-6 in paracrine tumor-stromal cell interactions in multiple myeloma

Dankbar, B., Padró, T., Leo, R., Feldmann, B., Kropff, M. H., Mesters, R. M., Serve, H. L., Berdel, W. E., & Kienast, J. (2000) · Blood · doi:10.1182/blood.v95.8.2630 · Cited by 568

Macrophages and cathepsin proteases blunt chemotherapeutic response in breast cancer

Shree, T., Olson, O. C., Elie, B. T., Kester, J. C., Garfall, A. L., Simpson, K., Bell-McGuinn, K. M., Zabor, E. C., Brogi, E., & Joyce, J. A. (2011) · Genes & Development · doi:10.1101/gad.180331.111 · Cited by 541

Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML

Zeng, Z., Shi, Y. X., Samudio, I. J., Wang, R., Ling, X., Frolova, O., Levis, M. J., Rubin, J. B., Negrin, R. S., Estey, E. H., et al. (2008) · Blood · doi:10.1182/blood-2008-05-158311 · Cited by 518

Endothelial expression of PD‐L1 and PD‐L2 down‐regulates CD8+ T cell activation and cytolysis

Rodig, N., Ryan, T., Allen, J. A., Pang, H. B., Grabie, N., Chernova, T., Greenfield, E. A., Liang, S. C., Sharpe, A. H., Lichtman, A. H., et al. (2003) · European Journal of Immunology · doi:10.1002/eji.200324270 · Cited by 503

Activation of fibroblasts in cancer stroma

Räsänen, K., & Vaheri, A. (2010) · Experimental Cell Research · doi:10.1016/j.yexcr.2010.04.032 · Cited by 499

G-CSF-initiated myeloid cell mobilization and angiogenesis mediate tumor refractoriness to anti-VEGF therapy in mouse models

Shojaei, F., Wu, X., Qu, X., Kowanetz, M., Yu, L., Tan, M., Meng, Y. G., & Ferrara, N. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0902280106 · Cited by 486

Imaging Tumor-Stroma Interactions during Chemotherapy Reveals Contributions of the Microenvironment to Resistance

Nakasone, E. S., Askautrud, H. A., Kees, T., Park, J.-H., Plaks, V., Ewald, A. J., Fein, M. R., Rasch, M. G., Tan, Y.-X., Qiu, J., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.017 · Cited by 485

PGE2-Induced CXCL12 Production and CXCR4 Expression Controls the Accumulation of Human MDSCs in Ovarian Cancer Environment

Obermajer, N., Muthuswamy, R., Odunsi, K. O., Edwards, R. P., & Kaliński, P. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-2449 · Cited by 480

Tumor-associated macrophages regulate tumorigenicity and anticancer drug responses of cancer stem/initiating cells

Jinushi, M., Chiba, S., Yoshiyama, H., Masutomi, K., Kinoshita, I., Dosaka-Akita, H., Yagita, H., Takaoka, A., & Tahara, H. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1106645108 · Cited by 479

A Phase I Study of an Agonist CD40 Monoclonal Antibody (CP-870,893) in Combination with Gemcitabine in Patients with Advanced Pancreatic Ductal Adenocarcinoma

Beatty, 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 456

Autophagy and cellular immune responses

Ma, Y., Galluzzi, L., Zitvogel, L., & Kroemer, G. (2013) · Immunity · doi:10.1016/j.immuni.2013.07.017 · Cited by 447

An interleukin-17-mediated paracrine network promotes tumor resistance to anti-angiogenic therapy

Chung, A. S., Wu, X., Zhuang, G., Ngu, H., Kasman, I., Zhang, J., Vernes, J.-M., Jiang, Z., Meng, Y. G., Peale, F. V., et al. (2013) · Nature Medicine · doi:10.1038/nm.3291 · Cited by 445

Mechanism of All- Trans Retinoic Acid Effect on Tumor-Associated Myeloid-Derived Suppressor Cells

Nefedova, Y., Fishman, M., Sherman, S., Wang, X., Beg, A. A., & Gabrilovich, D. I. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-2593 · Cited by 428

Phase 2 study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 (CCL2), in metastatic castration-resistant prostate cancer

Pienta, K. J., Machiels, J.-P., Schrijvers, D. L. A. L., Alekseev, B. Y., Shkolnik, M. I., Crabb, S. J., Li, S., Seetharam, S., Puchalski, T. A., Takimoto, C. H. M., et al. (2012) · Investigational New Drugs · doi:10.1007/s10637-012-9869-8 · Cited by 413

Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration

Podar, K., Tai, Y., Davies, F. E., Lentzsch, S., Sattler, M., Hideshima, T., Lin, B. K., Gupta, D. K., Shima, Y., Chauhan, D., et al. (2001) · Blood · doi:10.1182/blood.v98.2.428 · Cited by 412

Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature

Guetz, G. D., Uzzan, B., Nicolas, P., Cucherat, M., Morère, J., Benamouzig, R., Breau, J. L., & Perret, G.-Y. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6603176 · Cited by 406

IL-6 triggers cell growth via the Ras-dependent mitogen-activated protein kinase cascade

Ogata, A., Chauhan, D., Teoh, G. K. H., Treon, S. P., Urashima, M., Schlossman, R. L., & Anderson, K. C. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.5.2212 · Cited by 399

A phase 1/2 study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory acute myeloid leukemia

Uy, G. L., Rettig, M. P., Motabi, I., McFarland, K., Trinkaus, K. M., Hladnik, L. M., Kulkarni, S., Abboud, C. N., Cashen, A. F., Stockerl-Goldstein, K. E., et al. (2012) · Blood · doi:10.1182/blood-2011-10-383406 · Cited by 399

COX-2 Blockade Suppresses Gliomagenesis by Inhibiting Myeloid-Derived Suppressor Cells

Fujita, M., Kohanbash, G., Fellows-Mayle, W. K., Hamilton, R. L., Komohara, Y., Decker, S. A., Ohlfest, J. R., & Okada, H. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-3055 · Cited by 386

Targeting distinct tumor-infiltrating myeloid cells by inhibiting CSF-1 receptor: combating tumor evasion of antiangiogenic therapy

Priceman, S. J., Sung, J. L., Shaposhnik, Z., Burton, J. B., Torres‐Collado, A. X., Moughon, D. L., Johnson, M., Lusis, A. J., Cohen, D. A., Iruela‐Arispe, M. L., et al. (2009) · Blood · doi:10.1182/blood-2009-08-237412 · Cited by 370

CSF1R inhibition with emactuzumab in locally advanced diffuse-type tenosynovial giant cell tumours of the soft tissue: a dose-escalation and dose-expansion phase 1 study

Cassier, P. A., Italiano, A., Gomez‐Roca, C., Tourneau, C. L., Toulmonde, M., Cannarile, M. A., Ries, C. H., Brillouet, A., Müller, C., Jegg, A.-M., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00132-1 · Cited by 367

Chemotherapy Alters Monocyte Differentiation to Favor Generation of Cancer-Supporting M2 Macrophages in the Tumor Microenvironment

Dijkgraaf, E. M., Heusinkveld, M., Tummers, B., Vogelpoel, L. T. C., Goedemans, R., Jha, V., Nortier, J. W. R., Welters, M. J. P., Kroep, J. R., & van der Burg, S. H. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-3542 · Cited by 346

Interleukin 4 protects chronic lymphocytic leukemic B cells from death by apoptosis and upregulates Bcl-2 expression.

Dancescu, M., Rubio, M., Biron, G., Bron, D., Delespesse, G., & Sarfati, M. (1992) · The Journal of Experimental Medicine · doi:10.1084/jem.176.5.1319 · Cited by 344

Remodeling of the extracellular matrix through overexpression of collagen VI contributes to cisplatin resistance in ovarian cancer cells

Sherman‐Baust, C. A., Weeraratna, A. T., Rangel, L. B. A., Pizer, E. S., Cho, K. R., Schwartz, D. R., Shock, T. L., & Morin, P. J. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00058-8 · Cited by 340

Integrin signaling inhibits paclitaxel-induced apoptosis in breast cancer cells

Aoudjit, F., & Vuori, K. (2001) · Oncogene · doi:10.1038/sj.onc.1204554 · Cited by 336

HER2 signaling pathway activation and response of breast cancer cells to HER2-targeting agents is dependent strongly on the 3D microenvironment

Weigelt, B., Lo, A. T., Park, C. C., Gray, J. W., & Bissell, M. J. (2009) · Breast Cancer Research and Treatment · doi:10.1007/s10549-009-0502-2 · Cited by 334

Interferon‐γ reverses the immunosuppressive and protumoral properties and prevents the generation of human tumor‐associated macrophages

Duluc, D., Corvaisier, M., Blanchard, S., Catala, L., Descamps, P., Gamelin, E. C., Ponsoda, S., Delneste, Y., Hebbar, M., & Jeannin, P. (2009) · International Journal of Cancer · doi:10.1002/ijc.24401 · Cited by 328

Therapeutic regulation of myeloid-derived suppressor cells and immune response to cancer vaccine in patients with extensive stage small cell lung cancer

Iclozan, C., Antonia, S. J., Chiappori, A., Chen, D., & Gabrilovich, D. I. (2013) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-013-1396-8 · Cited by 326

Nurselike cells express BAFF and APRIL, which can promote survival of chronic lymphocytic leukemia cells via a paracrine pathway distinct from that of SDF-1α

Nishio, M., Endo, T., Tsukada, N., Ohata, J., Kitada, S., Reed, J. C., Zvaifler, N. J., & Kipps, T. J. (2005) · Blood · doi:10.1182/blood-2004-03-0889 · Cited by 321

Tumor angiogenesis is accompanied by a decreased inflammatory response of tumor-associated endothelium

Griffioen, A. W., Damen, C. A., Blijham, G. H., & Groenewegen, G. (1996) · Blood · doi:10.1182/blood.v88.2.667.bloodjournal882667 · Cited by 306

Small peptide inhibitors of the CXCR4 chemokine receptor (CD184) antagonize the activation, migration, and antiapoptotic responses of CXCL12 in chronic lymphocytic leukemia B cells

Burger, M., Hartmann, T. N., Krome, M., Rawluk, J. K., Tamamura, H., Fujii, N., Kipps, T. J., & Burger, J. A. (2005) · Blood · doi:10.1182/blood-2004-12-4918 · Cited by 295

Anti-inflammatory Triterpenoid Blocks Immune Suppressive Function of MDSCs and Improves Immune Response in Cancer

Nagaraj, S., Youn, J., Weber, H., Iclozan, C., Lu, L. D., Cotter, M. J., Meyer, C. J., Becerra, C. R., Fishman, M., Antonia, S. J., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-3272 · Cited by 286

Macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by upregulating cytidine deaminase

Weizman, N., Krelin, Y., Shabtay-Orbach, A., Amit, M., Binenbaum, Y., Wong, R. J., & Gil, Z. (2014) · Oncogene · doi:10.1038/onc.2013.357 · Cited by 281

MDSC as a mechanism of tumor escape from sunitinib mediated anti-angiogenic therapy

Finke, J. H., Ko, J. S., Rini, B. I., Rayman, P. A., Ireland, J. L., & Cohen, P. A. (2011) · International Immunopharmacology · doi:10.1016/j.intimp.2011.01.030 · Cited by 281

A first-in-human, first-in-class, phase I study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 in patients with solid tumors

Sandhu, S. K., Papadopoulos, K. P., Fong, P. C. C., Patnaik, A., Messiou, C., Olmos, D., Wang, G., Tromp, B. J., Puchalski, T. A., Balkwill, F. R., et al. (2013) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-013-2099-8 · Cited by 273

The Penetration of Anticancer Drugs through Tumor Tissue as a Function of Cellular Adhesion and Packing Density of Tumor Cells

Grantab, R., Sivananthan, S., & Tannock, I. F. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3077 · Cited by 254

Increase in tumor-associated macrophages after antiangiogenic therapy is associated with poor survival among patients with recurrent glioblastoma

Lu‐Emerson, C., Snuderl, M., Kirkpatrick, N. D., Goveia, J., Davidson, C. J., Huang, Y., Riedemann, L., Taylor, J. M., Ivy, P. S., Duda, D. G., et al. (2013) · Neuro-Oncology · doi:10.1093/neuonc/not082 · Cited by 235

Generation of a new therapeutic peptide that depletes myeloid-derived suppressor cells in tumor-bearing mice

Qin, H., Lerman, B., Sakamaki, I., Wei, G., Cha, S. C., Rao, S. S., Qian, J., Hailemichael, Y., Nurieva, R., Dwyer, K. C., et al. (2014) · Nature Medicine · doi:10.1038/nm.3560 · Cited by 234

Colony-Stimulating Factor-1 Antibody Reverses Chemoresistance in Human MCF-7 Breast Cancer Xenografts

Paulus, P., Stanley, E. R., Schäfer, R., Abraham, D., & Aharinejad, S. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3523 · Cited by 231

Regulation of Multidrug Resistance in Cancer Cells by Hyaluronan

Misra, S., Ghatak, S., Zoltan-Jones, A., & Toole, B. P. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.c300173200 · Cited by 225

Tumor Endothelial Cells Express Epidermal Growth Factor Receptor (EGFR) but not ErbB3 and Are Responsive to EGF and to EGFR Kinase Inhibitors

Amin, D. N., Hida, K., Bielenberg, D. R., & Klagsbrun, M. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3387 · Cited by 225

β1 Integrin Inhibition Dramatically Enhances Radiotherapy Efficacy in Human Breast Cancer Xenografts

Park, C. C., Zhang, H. J., Yao, E. S., Park, C. J., & Bissell, M. J. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-6390 · Cited by 220

Carlumab, an anti-C-C chemokine ligand 2 monoclonal antibody, in combination with four chemotherapy regimens for the treatment of patients with solid tumors: an open-label, multicenter phase 1b study

Braña, I., Calles, A., LoRusso, P. M., Yee, L., Puchalski, T. A., Seetharam, S., Zhong, B., de Boer, C. J., Tabernero, J. M., & Calvo, E. (2014) · Targeted Oncology · doi:10.1007/s11523-014-0320-2 · Cited by 218

A Combination of Chemoimmunotherapies Can Efficiently Break Self-Tolerance and Induce Antitumor Immunity in a Tolerogenic Murine Tumor Model

Ko, H., Kim, Y., Kim, Y.-S., Chang, W., Ko, S., Chang, S., Sakaguchi, S., & Kang, C. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-4639 · Cited by 205

CXCR4 downregulation of let-7a drives chemoresistance in acute myeloid leukemia

Chen, Y., Jacamo, R. O., Konopleva, M. Y., Garzon, R., Croce, C. M., & Andreeff, M. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66553 · Cited by 202

Prognostic Value of Vascular Endothelial Growth Factor Expression in Patients with Lung Cancer: A Systematic Review with Meta-Analysis

Zhan, P., Wang, J., Lv, X.-J., Wang, Q., Qiu, L., Lin, X.-Q., Yu, L.-K., & Song, Y. (2009) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3181a97e31 · Cited by 191

A randomized phase 2 study of etaracizumab, a monoclonal antibody against integrin αvβ3, ± dacarbazine in patients with stage IV metastatic melanoma

Hersey, P., Sosman, J. A., O'Day, S. J., Richards, J. M., Bedikian, A. Y., Gonzalez, R. C., Sharfman, W. H., Weber, R. W., Logan, T. F., Buzoianu, M., et al. (2010) · Cancer · doi:10.1002/cncr.24821 · Cited by 190

Cytogenetic Abnormalities of Tumor-Associated Endothelial Cells in Human Malignant Tumors

Akino, T., Hida, K., Hida, Y., Tsuchiya, K., Freedman, D. A., Muraki, C., Ohga, N., Matsuda, K., Akiyama, K., Harabayashi, T., et al. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.090202 · Cited by 183

Sensitizing Protective Tumor Microenvironments to Antibody-Mediated Therapy

Pallasch, C. P., Leskov, I. B., Braun, C. J., Vorholt, D., Drake, A. C. B., Soto‐Feliciano, Y. M., Bent, E. H., Schwamb, J., Iliopoulou, B. P., Kutsch, N., et al. (2014) · Cell · doi:10.1016/j.cell.2013.12.041 · Cited by 177

Basic fibroblast growth factor (bFGF) upregulates the expression of bcl-2 in B cell chronic lymphocytic leukemia cell lines resulting in delaying apoptosis

König, A. A., Menzel, T., Lynen, S., Wrazel, L., Rosén, A., Al-Katib, A. M., Raveche, E. S., & Jl, G. (1997) · Leukemia · doi:10.1038/sj.leu.2400556 · Cited by 173

Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

Erez, N., Glanz, S., Raz, Y., Avivi, C., & Barshack, I. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.06.089 · Cited by 170

The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 inhibits growth and migration of multiple myeloma cells in the bone marrow microenvironment

Anderson, K. C. (2003) · European Journal Of Haematology · doi:10.1034/j.1600-0609.2003.01067.x · Cited by 166

Tumor Endothelial Cells Acquire Drug Resistance by MDR1 Up-Regulation via VEGF Signaling in Tumor Microenvironment

Akiyama, K., Ohga, N., Hida, Y., Kawamoto, T., Sadamoto, Y., Ishikawa, S., Maishi, N., Akino, T., Kondoh, M., Matsuda, A., et al. (2012) · The American Journal of Pathology · doi:10.1016/j.ajpath.2011.11.029 · Cited by 154

Insulinlike growth factor–I signaling in multiple myeloma: downstream elements, functional correlates, and pathway cross-talk

Qiang, Y., Kopantzev, E. P., & Rudikoff, S. (2002) · Blood · doi:10.1182/blood.v99.11.4138 · Cited by 150

Phase 1B study to improve immune responses in head and neck cancer patients using escalating doses of 25-hydroxyvitamin D 3

Lathers, D. M. R., Clark, J. I., Achille, N. J., & Young, M. R. (2004) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-003-0459-7 · Cited by 149

Fibroblast-mediated drug resistance in cancer

Paraiso, K. H. T., & Smalley, K. S. M. (2013) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.01.018 · Cited by 147

Direct in vivo measurement of targeted binding in a human tumor xenograft

Berk, D. A., Fan, Y., Leunig, M., & Jain, R. K. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.5.1785 · Cited by 145

ECM overrides DNA damage-induced cell cycle arrest and apoptosis in small-cell lung cancer cells through β1 integrin-dependent activation of PI3-kinase

Hodkinson, P. S., Elliott, T., Wong, W. S., Rintoul, R. C., MacKinnon, A. C., Haslett, C., & Sethi, T. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401849 · Cited by 144

Anti‐ IL ‐6 receptor m A b eliminates myeloid‐derived suppressor cells and inhibits tumor growth by enhancing T ‐cell responses

Sumida, K., Wakita, D., Narita, Y., Masuko, K., Terada, S., Watanabe, K., Satoh, T., Kitamura, H., & Nishimura, T. (2012) · European Journal of Immunology · doi:10.1002/eji.201142335 · Cited by 131

Paracrine interactions of basic fibroblast growth factor and interleukin-6 in multiple myeloma

Bisping, G., Leo, R., Wenning, D., Dankbar, B., Padró, T., Kropff, M. H., Scheffold, C., Kröger, M., Mesters, R. M., Berdel, W. E., et al. (2003) · Blood · doi:10.1182/blood-2002-09-2907 · Cited by 127

Integrin alpha4 blockade sensitizes drug resistant pre-B acute lymphoblastic leukemia to chemotherapy

Hsieh, Y., Gang, E. J., Geng, H., Park, E., Huantes, S., Chudziak, D., Dauber, K., Schaefer, P., Scharman, C. D., Shimada, H., et al. (2013) · Blood · doi:10.1182/blood-2012-01-406272 · Cited by 124

On the origin of cancer-associated fibroblasts

Anderberg, C., & Pietras, K. (2009) · Cell Cycle · doi:10.4161/cc.8.10.8557 · Cited by 124

Enhancement of paclitaxel and carboplatin therapies by CCL2 blockade in ovarian cancers

Moisan, F., Francisco, E. B., Brozović, A., Durán, G. E., Wang, Y. C., Chaturvedi, S., Seetharam, S., Snyder, L. A., Doshi, P. D., & Sikic, B. I. (2014) · Molecular Oncology · doi:10.1016/j.molonc.2014.03.016 · Cited by 122

Lapatinib and doxorubicin enhance the S tat1‐dependent antitumor immune response

Hannesdóttir, L., Tymoszuk, P., Parajuli, N., Wasmer, M.-H., Philipp, S., Daschil, N., Datta, S., Koller, J., Tripp, C. H., Stoitzner, P., et al. (2013) · European Journal of Immunology · doi:10.1002/eji.201242505 · Cited by 113

Interferon‐alpha up‐regulates bcl‐2 expression and protects B‐CLL cells from apoptosis in vitro and in vivo

Jewell, A. P., Worman, C. P., Lydyard, P. M., Yong, K., Giles, F. J., & Goldstone, A. H. (1994) · British Journal of Haematology · doi:10.1111/j.1365-2141.1994.tb05017.x · Cited by 107

Antitumor Efficacy of the Anti-Interleukin-6 (IL-6) Antibody Siltuximab in Mouse Xenograft Models of Lung Cancer

Song, L., Smith, M. A., Doshi, P. D., Sasser, K., Fulp, W. J., Altiok, S., & Haura, E. B. (2014) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000193 · Cited by 100

Tenascin-C promotes melanoma progression by maintaining the ABCB5-positive side population

Fukunaga‐Kalabis, M., Martinez, G., Nguyen, T. K., Kim, D., Santiago-Walker, A., Roesch, A., & Herlyn, M. (2010) · Oncogene · doi:10.1038/onc.2010.350 · Cited by 94

Paracrine SDF-1α signaling mediates the effects of PSCs on GEM chemoresistance through an IL-6 autocrine loop in pancreatic cancer cells

Zhang, H., Wu, H., Guan, J., Wang, L., Ren, X., Shi, X., Liang, Z., & Liu, T. (2014) · Oncotarget · doi:10.18632/oncotarget.3099 · Cited by 93

Engagement of alpha4beta1 integrin by fibronectin induces in vitro resistance of B chronic lymphocytic leukemia cells to fludarabine.

de la Fuente, M. T., Casanova, B., Moyano, J. V., Garcı́a-Gila, M., Sanz, L., Garcia-Marco, J. A., Silva, A., & Garcı́a-Pardo, A. (2002) · PubMed · Cited by 90

Anti-vascular endothelial growth factor therapy-induced glioma invasion is associated with accumulation of Tie2-expressing monocytes

Gabrusiewicz, K. R., Liu, D., Cortes‐Santiago, N., Hossain, M. B., Conrad, C. A., Aldape, K., Fuller, G. N., Marini, F. C., Alonso, M. M., Idoate, M. A., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.1893 · Cited by 88

Phase II study of Cilengitide (EMD 121974, NSC 707544) in patients with non-metastatic castration resistant prostate cancer, NCI-6735. A study by the DOD/PCF prostate cancer clinical trials consortium

Alva, A. S., Slovin, S. F., Daignault, S. D., Carducci, M. A., DiPaola, R. S., Pienta, K. J., Agus, D. B., Cooney, K. A., Chen, A. P., Smith, D. C., et al. (2010) · Investigational New Drugs · doi:10.1007/s10637-010-9573-5 · Cited by 88

Engagement of α4β1 integrin by fibronectin induces in vitro resistance of B chronic lymphocytic leukemia cells to fludarabine

de la Fuente, M. T., Casanova, B., Moyano, J. V., Garcı́a-Gila, M., Sanz, L., Garcia-Marco, J. A., Silva, A., & Garcı́a-Pardo, A. (2002) · Journal of Leukocyte Biology · doi:10.1189/jlb.71.3.495 · Cited by 82

The selective adhesion molecule inhibitor Natalizumab decreases multiple myeloma cell growth in the bone marrow microenvironment: therapeutic implications

Podar, K., Zimmerhackl, A., Fulciniti, M., Tonon, G., Hainz, U., Tai, Y., Vallet, S., Halama, N., Jäger, D., Olson, D. L., et al. (2011) · British Journal of Haematology · doi:10.1111/j.1365-2141.2011.08864.x · Cited by 76

A phase 1 study of a chimeric monoclonal antibody against interleukin-6, siltuximab, combined with docetaxel in patients with metastatic castration-resistant prostate cancer

Hudes, G., Tagawa, S., Whang, Y., Qi, M., Qin, X., Puchalski, T., Reddy, M., Cornfeld, M., & Eisenberger, M. (2013) · Investigational new drugs · doi:10.1007/s10637-012-9857-z · Cited by 71

The Disintegrin-like and Cysteine-rich domains of ADAM-9 Mediate Interactions between Melanoma Cells and Fibroblasts

Zigrino, P., Nischt, R., & Mauch, C. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.168617 · Cited by 62

Lymph Node Stromal Cells Enhance Drug-Resistant Colon Cancer Cell Tumor Formation through SDF-1α/CXCR4 Paracrine Signaling

Margolin, D. A., Silinsky, J., Grimes, C., Spencer, N. D., Aycock, M., Green, H., Cordova, J., Davis, N. K., Driscoll, T., & Li, L. (2011) · Neoplasia · doi:10.1593/neo.11324 · Cited by 60

Secretion of vascular endothelial growth factor by oral squamous cell carcinoma cells skews endothelial cells to suppress T-cell functions

Mulligan, J. K., Day, T. A., Gillespie, M. B., Rosenzweig, S. A., & Young, M. R. (2009) · Human Immunology · doi:10.1016/j.humimm.2009.01.014 · Cited by 56

Tumors induce the formation of suppressor endothelial cells in vivo

Mulligan, J. K., & Young, M. R. (2009) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-009-0747-y · Cited by 49

Inhibition of α4β1 integrin increases ovarian cancer response to carboplatin

Scalici, J. M., Harrer, C., Allen, A., Jazaeri, A. A., Atkins, K. A., McLachlan, K. R., & Slack‐Davis, J. K. (2014) · Gynecologic Oncology · doi:10.1016/j.ygyno.2013.12.031 · Cited by 36

Bortezomib, Dexamethasone, and Fibroblast Growth Factor Receptor 3–Specific Tyrosine Kinase Inhibitor in t(4;14) Myeloma

Bisping, G., Wenning, D., Kropff, M. H., Gustavus, D., Müller‐Tidow, C., Stelljes, M., Munzert, G. M., Hilberg, F., Roth, G. J., Štefanič, M., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-1612 · Cited by 33

Role of the extracellular matrix proteins in the resistance of SP6.5 uveal melanoma cells toward cisplatin

Bérubé, M., Talbot, M., Collin, C., Paquet‐Bouchard, C., Germain, L., Guérin, S. L., & Petitclerc, É. (2005) · International Journal of Oncology · doi:10.3892/ijo.26.2.405 · Cited by 30

Cilengitide treatment of newly diagnosed glioblastoma patients does not alter patterns of progression

Neyns, B. (2014) · VUBIR (Vrije Universiteit Brussel) · doi:10.1007/s11060-014-1365-x

Role of hypoxia in cancer therapy by regulating the tumor microenvironment

Jing, X., Yang, F., Shao, C., Wei, K., Xie, M., Shen, H., & Shu, Y. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1089-9 · Cited by 2,054

The rediscovery of platinum-based cancer therapy

Rottenberg, S., Disler, C., & Perego, P. (2020) · Nature reviews. Cancer · doi:10.1038/s41568-020-00308-y · Cited by 993

Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Zhang, Z., Liu, X., Chen, D., & Yu, J. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01102-y · Cited by 736

The application of nanoparticles in cancer immunotherapy: Targeting tumor microenvironment

Yang, M., Li, J., Gu, P., & Fan, X. (2020) · Bioactive Materials · doi:10.1016/j.bioactmat.2020.12.010 · Cited by 688

Shaping Polarization Of Tumor-Associated Macrophages In Cancer Immunotherapy

Gao, J., Liang, Y., & Wang, L. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.888713 · Cited by 586

Microenvironmental regulation of therapeutic response in cancer

Klemm, F., & Joyce, J. A. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.11.006 · Cited by 795

Tumor microenvironment as a therapeutic target in cancer

Xiao, Y. Q., & Yu, D. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107753 · Cited by 2,026

From immune exclusion to exhaustion: tumor microenvironment drives therapy response

Maletin, N. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1785587 · Cited by 16

Tumor Microenvironment and Drug Response: A Pathology–pharmacology Perspective on Mechanisms of Therapeutic Resistance

Ravichandran, S., & Vilvanathan, S. (2026) · doi:10.9734/ajmpcp/2026/v9i1402

Potential Strategies to Improve the Effectiveness of Drug Therapy by Changing Factors Related to Tumor Microenvironment

Cao, D., Naiyila, X., Li, J., Huang, Y. C., Chen, Z., Chen, B., Li, J., Guo, J., Dong, Q., Ai, J., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.705280 · Cited by 7