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NKG2D Ligand Expression in Human Colorectal Cancer Reveals Associations with Prognosis and Evidence for Immunoediting
Open accessAbstract
Purpose: NKG2D (natural killer group 2, member D) binds to cellular ligands of the MIC and ULBP/RAET family. These ligands have restricted expression in normal tissue, but are frequently expressed on primary tumors. The role of NKG2D ligands is thought to be important in carcinogenesis but its prognostic effect has not been investigated in such a large cohort. Experimental Design: In our study, 462 primary colorectal tumors were screened for the expression of all MIC/ULBP/RAET proteins and NK cell infiltration. Tumor microarray technology was used for the purpose of this investigation. Results: NKG2D ligands were expressed by the majority of colorectal tumors; however, the level of expression varied considerably. High expression of MIC (68 versus 56 months) or RAET1G (74 versus 62 months) showed improved patient survival. Tumors expressing high levels of MIC and RAET1G showed improved survival of 77 months over tumors that expressed high levels of one ligand or low levels of both. High-level expression of all ligands was frequent in tumor-node-metastasis stage I tumors, but became progressively less frequent in stages II, III, and IV tumors. Expression of MIC was correlated with NK cellular infiltration. Conclusion: The observations presented are consistent with an immunoediting mechanism that selects tumor cells that have lost or reduced their expression of NKG2D ligands. The combination of MIC and tumor-node-metastasis stage was found to be the strongest predictor of survival, splitting patients into eight groups and suggesting prognostic value in clinical assessment. Of particular interest were stage I patients with low expression of MIC who had a similar survival to stage III patients, and may be candidates for adjuvant therapy. (Clin Cancer Res 2009;15(22):69937002)
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“These findings may be one explanation for why expression of NKG2D ligands in some cancers is insufficient to trigger NKG2D-dependent elimination of tumors (Jinushi et al., 2003; Guerra et al., 2008; McGilvray et al., 2009; Hilpert et al., 2012).”
From p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells (2013) · cites this paper as McGilvray et al., 2009
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Self-citationPerturbation of NK cell peripheral homeostasis accelerates prostate carcinoma metastasis
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Reduced NKG2D ligand expression in hepatocellular carcinoma correlates with early recurrence
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Guzman, L. G. M., Keating, N., & Nicholson, S. E. (2020) · Cancers · doi:10.3390/cancers12040952 · Cited by 118
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BackgroundTumor-associated autoantibodies as diagnostic and prognostic biomarkers
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Self-citationDysfunctional Natural Killer Cells in the Aftermath of Cancer Surgery
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“Although the ligands for these receptors are poorly defined and a topic of considerable interest, recent work has determined that NKG2D recognizes cell surface glycoproteins (including MHC-class I polypeptide-related sequence A (MICA), MICB, UL16-binding proteins 1–6 (ULPBs)) and NCRs bind heparin sulfate [29,30].”
BackgroundMechanisms of Immunosuppression in Colorectal Cancer
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“Another clinical study has demonstrated that the survival advantage of CRC may differ because of the different expression patterns of two groups of NKG2D ligands (MIC and RAET1G) in the tumor cells, suggesting that some expression signature of NKG2D ligands in tumor cells may inhibit the activation of NK cells and ind…”
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Immunobiology and Conflicting Roles of the Human NKG2D Lymphocyte Receptor and Its Ligands in Cancer
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BackgroundDevelopment of NKG2D-based chimeric antigen receptor-T cells for gastric cancer treatment
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“NKG2D ligands are highly expressed by CRC tumors, especially in their early stages, but are progressively lost, and their expression levels correlate with patient survival [26].”
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“This observation suggest that aggressive metastasis could become also resistant to NK cells by losing the expression of ligands for those activating receptors, and this has been reported in some clinical studies.(40) In addition, it has been reported that in vivo, NK cells could lack migration inside the tumor mass, e…”
Cadoux, M., Caruso, S., Pham, S., Gougèlet, A., Pophillat, C., Riou, R., Loesch, R., Colnot, S., Nguyễn, C. T., Caldéraro, J., et al. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.01.017 · Cited by 75
Opposite effects of microchimerism on breast and colon cancer
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“As another example NKG2D-family ligand overexpression represents a tumour immune evasion strategy for most tumours including breast,(39) but is associated with better prognosis in colorectal cancer.(40) If confirmed, our findings may be clinically exploitable as a prescreening test to identify women with a high freque…”
BackgroundMolecular Bases for the Regulation of NKG2D Ligands in Cancer
Huergo-Zapico, L., Acebes‐Huerta, A., López‐Soto, A., Villa-Ãlvarez, M. N., González, A. P., & Gonzalez, S. R. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00106 · Cited by 66
“Moreover, cell-associated NKG2DL expression correlates with the outcome in colorectal (16, 17), breast, (18) and pancreatic cancers (19) and hepatocellular carcinoma (20).”
BackgroundCancer Immunosurveillance and Immunoediting by Natural Killer Cells
Gross, E. T. E., Sunwoo, J. B., & Bui, J. D. (2013) · The Cancer Journal · doi:10.1097/ppo.0000000000000005 · Cited by 68
“In a study of 462 primary colorectal carcinoma tumors, a significant positive correlation between NKG2D ligand expression on the tumor cells and better survival was observed.(91) Importantly, the expression of NKG2D ligands was progressively lower in higher-staged tumors, and this was associated with a decreased immun…”
BackgroundHigh levels of cleaved caspase-3 in colorectal tumour stroma predict good survival
Noble, P. W., Vyas, M., Al‐Attar, A., Durrant, S., Scholefield, J. H., & Durrant, L. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.166 · Cited by 66
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BackgroundSelf-citationBalanced engagement of activating and inhibitory receptors mitigates human NK cell exhaustion
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The Paradoxical Role of NKG2D in Cancer Immunity
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“One common feature is the heterogeneity in ligand expression between cancer types and individuals (42, 45, 47, 51), which hinders the prognostic value of NKG2D ligands in clinical assessment.”
BackgroundRegulation of NKG2D Stress Ligands and Its Relevance in Cancer Progression
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Loss of natural killer T cells promotes pancreatic cancer in LSL ‐KrasG12D/+ mice
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Modulation of NKG2D ligand expression and metastasis in tumors by spironolactone via RXRγ activation
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“The ligand expression, however, progressively decreases in later stages of the disease, and the level of expression correlates with patient survival (McGilvray et al., 2009).”
BackgroundExploiting natural killer group 2D receptors for CAR T-cell therapy
Demoulin, B., Cook, W. J., Murad, J., Graber, D. J., Sentman, M.-L., Lonez, C., Gilham, D. E., Sentman, C. L., & Agaugué, S. (2017) · Future Oncology · doi:10.2217/fon-2017-0102 · Cited by 58
Mucosa-associated invariant T cells in malignancies: a faithful friend or formidable foe?
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“It binds to proteins encoded by the MHC class I polypeptide-related sequence (MIC) A and B loci and members of the UL16-binding protein/ retinoic acid early transcript 1 (ULBP/RAET1) family [66, 67].”
Therapeutic potential of highly cytotoxic natural killer cells for gastric cancer
Mimura, K., Kamiya, T., Shiraishi, K., Kua, L., Shabbir, A., So, J. B. Y., Yong, W. P., Suzuki, Y., Yoshimoto, Y., Nakano, T., et al. (2014) · International Journal of Cancer · doi:10.1002/ijc.28780 · Cited by 56
Gowen, B. G., Chim, B., Marceau, C. D., Greene, T. T., Burr, P., Gonzalez, J. R., Hesser, C. R., Dietzen, P. A., Russell, T. A., Iannello, A., et al. (2015) · eLife · doi:10.7554/elife.08474 · Cited by 52
“In the case of NKG2Dmediated tumor recognition, published results suggest that one mechanism of tumor immune evasion is the loss or decreased expression of NKG2D ligands (Guerra et al., 2008; McGilvray et al., 2009).”
BackgroundT-Cell-Based Immunotherapy for Osteosarcoma: Challenges and Opportunities
Wang, Z., Li, B., Ren, Y., & Ye, Z. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00353 · Cited by 73
“A positive correlation between NKG2D-L expression and improved clinical outcomes has been documented in various solid tumors (138).”
BackgroundZaghi, E., Calvi, M., Marcenaro, E., Mavilio, D., & Vito, C. D. (2019) · Journal of Leukocyte Biology · doi:10.1002/jlb.mr0718-300r · Cited by 53
Assessment of the humoral immune response to cancer
Murphy, M., O’Leary, J. J., & Cahill, D. J. (2012) · Journal of Proteomics · doi:10.1016/j.jprot.2012.01.021 · Cited by 51
“[11] McGilvray RW, Eagle RA,Watson NF, Al-Attar A, Ball G, Jafferji I, et al.”
BackgroundExploiting NK Cell Surveillance Pathways for Cancer Therapy
Barrow, A., & Colonna, M. (2019) · Cancers · doi:10.3390/cancers11010055 · Cited by 48
Guma, S. R., Lee, D. A., Yu, L., Gordon, N. B., Hughes, D. P. M., Stewart, J., Wang, W., & Kleinerman, E. S. (2013) · Pediatric Blood & Cancer · doi:10.1002/pbc.24801 · Cited by 50
“Usually decreased NKG2DL expression correlates with disease progression [33].”
BackgroundNieto-Velázquez, N. G., Torres-Ramos, Y. D., Muñoz-Sánchez, J. L., Espinosa-Godoy, L., Gómez-Cortés, S., Moreno, J. G., & Moreno‐Eutímio, M. A. (2016) · Translational Oncology · doi:10.1016/j.tranon.2016.07.003 · Cited by 49
“There were no significant differences in the absolute numbers or percentages of white blood cells, CD4+T cells, CD8+T cells, B cells, NK cells,monocytes, eosinophils, neutrophils, and basophils (Tables 3 and 4).”
BackgroundThe Role and Regulation of the NKG2D/NKG2D Ligand System in Cancer
Tan, G., Spillane, K. M., & Maher, J. F. (2023) · Biology · doi:10.3390/biology12081079 · Cited by 56
Vacca, P., Martini, S., Garelli, V., Passalacqua, G., Moretta, L., & Mingari, M. C. (2012) · European Journal of Immunology · doi:10.1002/eji.201242783 · Cited by 45
Vyas, M., Reinartz, S., Hoffmann, N., Reiners, K., Lieber, S., Jansen, J. M., Wagner, U., Müller, R., & von Strandmann, E. P. (2017) · Oncoimmunology · doi:10.1080/2162402x.2017.1339854 · Cited by 35
NK Cell-Based Immunotherapy in Colorectal Cancer
Chiesa, M. D., Setti, C., Giordano, C., Obino, V., Greppi, M., Pesce, S., Marcenaro, E., Rutigliani, M., Provinciali, N., Paleari, L., et al. (2022) · Vaccines · doi:10.3390/vaccines10071033 · Cited by 44
Huyan, T., Li, M., Wang, C., Chen, W., Zhou, X., Zhang, X., Duan, S., Gao, S., & Li, Q. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315177 · Cited by 48
“Exhausted anti-tumor immune function has been reported in numerous tumors, including breast cancer, lung cancer, colon cancer [8], kidney cancer, pancreatic cancer, ovarian cancer [9], glioma, and melanoma [10].”
BackgroundShiraishi, K., Mimura, K., Kua, L., Koh, V., Siang, L. K., Nakajima, S., Fujii, H., Shabbir, A., Yong, W. P., So, J. B. Y., et al. (2016) · Journal of Gastroenterology · doi:10.1007/s00535-016-1197-x · Cited by 43
Astragaloside III Enhances Anti-Tumor Response of NK Cells by Elevating NKG2D and IFN-γ
Chen, X.-M., Chen, X., Gao, J., Yang, H., Duan, Y., Feng, Y.-X., He, X., Gong, X.-Q., Wang, H.-J., Wu, X.-L., et al. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00898 · Cited by 41
“Clinical investigations have shown that high levels of NKG2D ligands on tumor cells predict favorable prognosis (Lanier, 2015), whereas reduced expression of NKG2D usually correlates with strong prognostic relevance in patients (McGilvray et al., 2009).”
Siew, Y.-Y., Neo, S.-Y., Yew, H.-C., Lim, S.-W., Ng, Y.-C., Lew, S.-M., Seetoh, W.-G., Seow, S.-V., & Koh, H. (2015) · International Immunology · doi:10.1093/intimm/dxv041 · Cited by 41
Tsukagoshi, M., Wada, S., Yokobori, T., Altan, B., Ishii, N., Watanabe, A., Kubo, N., Saito, F., Araki, K., Suzuki, H., et al. (2015) · Cancer Science · doi:10.1111/cas.12853 · Cited by 41
Zhang, Z., Su, T., He, L., Wang, H., Ji, G., Liu, X., Zhang, Y., & Dong, G. (2011) · The Tohoku Journal of Experimental Medicine · doi:10.1620/tjem.226.59 · Cited by 38
Fernández-Messina, L., Ashiru, O., Agüera-González, S., Reyburn, H., & Valés-Gómez, M. (2011) · Journal of Cell Science · doi:10.1242/jcs.076042 · Cited by 42
The Role of NKG2D and Its Ligands in Autoimmune Diseases: New Targets for Immunotherapy
Wei, L., Xiang, Z., & Zou, Y. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242417545 · Cited by 39
“Furthermore, high expression of NKG2D-L was associated with a good prognosis and improved tumor invasion in cancer patients [36,37].”
BackgroundLoss of CD 155 expression predicts poor prognosis in hepatocellular carcinoma
Qü, P., Huang, X., Zhou, X., Lu, Z.-M., Liu, F., Shi, Z., Lü, L., Wu, Y., & Chen, Y. (2014) · Histopathology · doi:10.1111/his.12584 · Cited by 33
“It has been demonstrated that the low expression levels of NK cell activation ligands such as major histocompatibilty complex (MHC) class I polypeptiderelated sequence A (MICA), MHC class I polypeptiderelated sequence B (MICB) and UL16 binding protein 1 (ULBP1) on tumour cells are associated with the progression of ca…”
BackgroundPurine nucleotide metabolism regulates expression of the human immune ligand MICA
McCarthy, M. T., Moncayo, G., Hiron, T. K., Jakobsen, N. A., Valli, A., Soga, T., Adam, J., & O’Callaghan, C. A. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.809459 · Cited by 33
“These results are consistent with observational studies of NKG2D ligand expression in disparate settings from malignancy (5) to viral infection (6, 7) and physiological cell proliferation (8, 9).”
BackgroundResultImmunotherapeutic targeting of activating natural killer cell receptors and their ligands in cancer
Peipp, M., Klausz, K., Boje, A. S., Zeller, T., Zielonka, S., & Kellner, C. (2022) · Clinical & Experimental Immunology · doi:10.1093/cei/uxac028 · Cited by 33
Ribeiro, C. H., Kramm, K., Gálvez‐Jirón, F., Pola-Véliz, V., BUSTAMANTE, M., Contreras, H. R., Sabag, A., Garrido‐Tapia, M., Hernández, C., ZÚÑIGA, R., et al. (2015) · Oncology Reports · doi:10.3892/or.2015.4510 · Cited by 32
“In colorectal and pancreatic cancers, MICA was detected as an independent marker of favorable prognosis for stages I and II, but not later stages of the disease (15,45).”
BackgroundCrystal Structure of the Cowpox Virus-Encoded NKG2D Ligand OMCP
Lazear, E., Peterson, L. W., Nelson, C. A., & Fremont, D. H. (2012) · Journal of Virology · doi:10.1128/jvi.01948-12 · Cited by 31
“Tumor cells expressing high levels of NKG2DLs are more susceptible to immune clearance, and NKG2DLs have been implicated in immunoediting of tumor cells (14, 15).”
BackgroundZitvogel, L., Kepp, O., Aymeric, L., Ma, Y., Locher, C., Delahaye, N. F., André, F., & Kroemer, G. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1003 · Cited by 31
Krijgsman, D., Roelands, J. P., Andersen, M. N., Wieringa, C. H. L. A., Tollenaar, R. A. �. �., Hendrickx, W., Bedognetti, D., Hokland, M., & Kuppen, P. J. K. (2020) · Molecular Immunology · doi:10.1016/j.molimm.2020.10.012 · Cited by 30
Immune ULBP1 is Elevated in Colon Adenocarcinoma and Predicts Prognosis
Ruan, G., Xie, H., Zhu, L., Ge, Y., Lin, Y., Liao, C., Gong, Y., & Shi, H. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.762514 · Cited by 29
“In humans, primary tumors and tumor cell lines express NKG2D ligands at a high frequency (McGilvray et al., 2009).”
BackgroundResultInfluentialMolecular Mechanisms of Tumor Immunomodulation in the Microenvironment of Colorectal Cancer
Plundrich, D., Chikhladze, S., Fichtner‐Feigl, S., Feuerstein, R., & Briquez, P. S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052782 · Cited by 31
“ligands are not generally expressed in healthy cells but are upregulated during carcinogenesis [40,41].”
BackgroundZhang, Y.-P., Liang, K.-J., Zhou, X., Zhang, X., Xu, H., Dai, H., Song, X., Yang, X., Liu, B.-R., Shi, T., et al. (2023) · Cancer Science · doi:10.1111/cas.15828 · Cited by 24
Targeting p53 for immune modulation: Exploring its functions in tumor immunity and inflammation
Wu, H. H., Leng, S., Eisenstat, D. D., Sergi, C. M., & Leng, R. P. (2025) · Cancer Letters · doi:10.1016/j.canlet.2025.217614 · Cited by 27
Sanchez, C. E., Dowlati, E. P., Geiger, A. E., Chaudhry, K., Tovar, M. A., Bollard, C. M., & Cruz, C. C. (2020) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2020.09.030 · Cited by 29
“Bottom, in blue: NK cell activating receptor ligands are expressed by numerous malignancies [45-60,62,242-247], and these tumors engage NK-activating receptors, some of which associate with ITAM-containing DAP10 and DAP12 to mediate NK cell activation via proteins such as Vav1 and PLCγ2.”
BackgroundOliviero, B., Varchetta, S., Mele, D., Pessino, G., Maiello, R., Falleni, M., Tosi, D., Donadon, M., Soldani, C., Franceschini, B., et al. (2022) · Oncoimmunology · doi:10.1080/2162402x.2022.2035919 · Cited by 31
“Furthermore, soluble MICA and MICB that might block NKG2D receptor interaction with its cellular ligands are found in the sera of cancer patients, which frequently correlate with poor prognosis and impaired T and NK cell function.(19,28) Recently, Ferrari de Andrade et al.”
BackgroundCancer Immunoediting: Elimination, Equilibrium, and Immune Escape in Solid Tumors
Wilczyński, J. R., & Nowak, M. (2022) · Experientia supplementum · doi:10.1007/978-3-030-91311-3_1 · Cited by 27
Li, B., Zhu, X., Ge, J., Zhang, H., Gao, Y., Bao, X., Dai, X., Du, Z., Tu, X., Zhou, T., et al. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.05.026 · Cited by 26
Insights Into Cetacean Immunology: Do Ecological and Biological Factors Make the Difference?
Marsili, L., Guardo, G. D., Mazzariol, S., & Casini, S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01219 · Cited by 25
“(37) reported that NKG2D ligands were highly expressed in lymph node metastasis of stage I colorectal cancer samples, but they were expressed in lower amounts in Stage II, III, or IV tumors.”
BackgroundKIM, G. R., Ha, G., BAE, J.-H., Oh, S., Kim, S., & Kang, C. (2015) · Oncology Letters · doi:10.3892/ol.2015.2918 · Cited by 25
“High expression of MIC or RAET1G has been shown to be associated with prolonged survival of patients with colorectal tumors (38).”
Singh, S., & Banerjee, S. (2020) · Scientific Reports · doi:10.1038/s41598-020-62081-0 · Cited by 25
PRL-3 Mediates the Protein Maturation of ULBP2 by Regulating the Tyrosine Phosphorylation of HSP60
Leung, W., Vong, Q. P., Lin, W., Bouck, D. C., Wendt, S., Sullivan, E., Li, Y., Bari, R., Chen, T., & Leung, W. H. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1400817 · Cited by 24
“Many reports have suggested that the expression level of NKG2DLs on tumor cells directly correlates with tumor susceptibility to NK cytolysis (2) and with cancer patient survival rate (3).”
BackgroundLebrec, H. N., Brennan, F. R., Haggerty, H. G., Herzyk, D., Kamperschroer, C., Maier, C. C., Ponce, R. A., Preston, B. D., Weinstock, D., & Mellon, R. D. (2015) · Regulatory Toxicology and Pharmacology · doi:10.1016/j.yrtph.2015.12.018 · Cited by 24
Hu, J., Bernatchez, C., Zhang, L., Xia, X., Kleinerman, E. S., Hung, M., Hwu, P., & Li, S. (2017) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-16-0234 · Cited by 24
“In colorectal cancer patients, large amounts of the NKG2D ligands MICA and ULBP2, in particular, were shown to correlate with a longer survival time (10).”
Harnessing Natural Killer Cells in Cancer Immunotherapy: A Review of Mechanisms and Novel Therapies
St‐Pierre, F., Bhatia, S., & Chandra, S. (2021) · Cancers · doi:10.3390/cancers13081988 · Cited by 24
“Nonetheless, tumor cells have developed mechanisms to evade destruction by NK cells; namely, certain tumor cells shed “decoy” NKG2D soluble ligands to saturate the NKG2D receptor on the NK cells to prevent the destruction of the tumor cells [16].”
Background
Metadata
- Authors
- McGilvray, R. W., Eagle, R. A., Watson, N. F. S., Al-Attar, A., Ball, G., Jafferji, I., Trowsdale, J., & Durrant, L. G.
- Affiliations
- University of Nottingham (GB)
- Authors' Affiliations: 1Academic Division of Clinical Oncology, University of Nottingham, City Hospital Campus, 2Section of Gastrointestinal Surgery, Queen's Medical Centre, 3John Van Geest Research Centre, Nottingham Trent University, Clifton Campus, Nottingham, United Kingdom, and 4Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrookes Hospital, Cambridge, United Kingdom
- Venue
- Clinical Cancer Research
- Published
- 2009-11-11
- Volume
- 15
- Issue
- 22
- Pages
- 6993-7002
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC2778653
- OpenAlex
- W2101699880
- Cited by
- 196
- References
- 46
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 8 · 2023: 13 · 2022: 18 · 2021: 13 · 2020: 13 · 2019: 13 · 2018: 8 · 2017: 10 · 2016: 6 · 2015: 17 · 2014: 18 · 2013: 14 · 2012: 10
- FWCI
- 3.74
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Nottingham Trent University's Institutional Repository (Nottingham Trent Repository) (submittedVersion)
- Funders
- Cancer Research UK (A7607)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- NKG2D ligands, colorectal cancer, NK cell infiltration, immunoediting, prognostic factors, patient survival, tumor stage, adjuvant therapy
- MeSH terms
- Aged, Female, Humans, Immunohistochemistry, Ligands, Male, Middle Aged, Models, Theoretical, Neoplasm Metastasis, Prognosis, Time Factors, Colorectal Neoplasms, Cohort Studies, Proportional Hazards Models, Treatment Outcome, Disease-Free Survival, Oligonucleotide Array Sequence Analysis, NK Cell Lectin-Like Receptor Subfamily K
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