MHC-II neoantigens shape tumour immunity and response to immunotherapy
Open accessAbstract
The ability of the immune system to eliminate and shape the immunogenicity of tumours defines the process of cancer immunoediting 1. Immunotherapies such as those that target immune checkpoint molecules can be used to augment immune-mediated elimination of tumours and have resulted in durable responses in patients with cancer that did not respond to previous treatments. However, only a subset of patients benefit from immunotherapy and more knowledge about what is required for successful treatment is needed 2-4. Although the role of tumour neoantigen-specific CD8+ T cells in tumour rejection is well established 5-9, the roles of other subsets of T cells have received less attention. Here we show that spontaneous and immunotherapy-induced anti-tumour responses require the activity of both tumour-antigen-specific CD8+ and CD4+ T cells, even in tumours that do not express major histocompatibility complex (MHC) class II molecules. In addition, the expression of MHC class II-restricted antigens by tumour cells is required at the site of successful rejection, indicating that activation of CD4+ T cells must also occur in the tumour microenvironment. These findings suggest that MHC class II-restricted neoantigens have a key function in the anti-tumour response that is nonoverlapping with that of MHC class I-restricted neoantigens and therefore needs to be considered when identifying patients who will most benefit from immunotherapy.
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HLA class I and class II molecules are centrally involved in CD8+ and CD4+ T cell immunity.
“As both classes of HLA molecule have previously been shown to have a central role in CD8+ and CD4+ T cell immunity43–49”
From Identification of bacteria-derived HLA-bound peptides in melanoma (2021) · cites this paper as [46]
MHC class II neoantigens participate in effective tumor responses.
“MHC class II neoantigens are also involved in effective tumor responses”
From The Next Decade of Immune Checkpoint Therapy (2021) · cites this paper as [218]
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Cites
Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer
Borghaei, H., Paz-Ares, L., Horn, L., Spigel, D. R., Steins, M., Ready, N. E., Chow, L. Q., Vokes, E. E., Felip, E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1507643 · Cited by 9,335 · see citing works
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma
Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J. J., Cowey, C. L., Lao, C. D., Schadendorf, D., Dummer, R., Smylie, M., Rutkowski, P., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504030 · Cited by 8,157 · see citing works
Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer
Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J. J., Lee, W., Yuan, J., Wong, P., Ho, T. S., et al. (2015) · Science · doi:10.1126/science.aaa1348 · Cited by 7,802 · see citing works
Cancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion
Schreiber, R. D., Old, L. J., & Smyth, M. J. (2011) · Science · doi:10.1126/science.1203486 · Cited by 6,474 · see citing works
Self-citationNivolumab versus Everolimus in Advanced Renal-Cell Carcinoma
Motzer, R. J., Escudier, B., McDermott, D. F., George, S., Hammers, H. J., Srinivas, S., Tykodi, S. S., Sosman, J. A., Procopio, G., Plimack, E. R., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1510665 · Cited by 5,807 · see citing works
Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma
Snyder, A., Makarov, V., Merghoub, T., Yuan, J., Zaretsky, J. M., Desrichard, A., Walsh, L. A., Postow, M. A., Wong, P., Ho, T. S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1406498 · Cited by 4,286 · see citing works
Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma
Hugo, W., Zaretsky, J. M., Sun, L., Song, C., Moreno, B. H., Hu-Lieskovan, S., Berent-Maoz, B., Pang, J., Chmielowski, B., Cherry, G., et al. (2016) · Cell · doi:10.1016/j.cell.2016.02.065 · Cited by 3,448 · see citing works
An immunogenic personal neoantigen vaccine for patients with melanoma
Ott, P. A., Hu, Z., Keskin, D. B., Shukla, S. A., Sun, J., Bozym, D. J., Zhang, W., Luoma, A., Giobbie-Hurder, A., Peter, L., et al. (2017) · Nature · doi:10.1038/nature22991 · Cited by 2,936 · see citing works
Self-citationGenomic correlates of response to CTLA-4 blockade in metastatic melanoma
Van Allen, E. M., Miao, D., Schilling, B., Shukla, S. A., Blank, C., Zimmer, L., Sucker, A., Hillen, U., Geukes Foppen, M. H., Goldinger, S. M., et al. (2015) · Science · doi:10.1126/science.aad0095 · Cited by 2,839 · see citing works
Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens
Gubin, M. M., Zhang, X., Schuster, H., Caron, E., Ward, J. P., Noguchi, T., Ivanova, Y., Hundal, J., Arthur, C. D., Krebber, W.-J., et al. (2014) · Nature · doi:10.1038/nature13988 · Cited by 1,974 · see citing works
Self-citationCancer Immunotherapy Based on Mutation-Specific CD4+ T Cells in a Patient with Epithelial Cancer
Tran, E., Turcotte, S., Gros, A., Robbins, P. F., Lu, Y., Dudley, M. E., Wunderlich, J. R., Somerville, R. P. T., Hogan, K., Hinrichs, C. S., et al. (2014) · Science · doi:10.1126/science.1251102 · Cited by 1,710 · see citing works
CD4+ T cell help in cancer immunology and immunotherapy
Borst, J., Ahrends, T., Bąbała, N., Melief, C. J. M., & Kastenmüller, W. (2018) · Nature Reviews Immunology · doi:10.1038/s41577-018-0044-0 · Cited by 1,585 · see citing works
Jurtz, V. I., Paul, S., Andreatta, M., Marcatili, P., Peters, B., & Nielsen, M. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700893 · Cited by 1,476 · see citing works
Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade
Wei, S. C., Levine, J. H., Cogdill, A. P., Zhao, Y., Anang, N.-A. A. S., Andrews, M. C., Sharma, P., Wang, J., Wargo, J. A., Pe’er, D., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.024 · Cited by 1,302 · see citing works
Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting
Matsushita, H., Vesely, M. D., Koboldt, D. C., Rickert, C. G., Uppaluri, R., Magrini, V. J., Arthur, C. D., White, J. M., Chen, Y.-S., Shea, L. K., et al. (2012) · Nature · doi:10.1038/nature10755 · Cited by 1,285 · see citing works
Self-citationMutant MHC class II epitopes drive therapeutic immune responses to cancer
Kreiter, S., Vormehr, M., van de Roemer, N., Diken, M., Löwer, M., Diekmann, J., Boegel, S., Schrörs, B., Vascotto, F., Castle, J. C., et al. (2015) · Nature · doi:10.1038/nature14426 · Cited by 1,243 · see citing works
A p16 INK4a -Insensitive CDK4 Mutant Targeted by Cytolytic T Lymphocytes in a Human Melanoma
Wölfel, T., Hauer, M., Schneider, J., Serrano, M., Wölfel, C., Klehmann, E., Plaen, E. D., Hankeln, T., Büschenfelde, K. M. Z., & Beach, D. (1995) · Science · doi:10.1126/science.7652577 · Cited by 1,153 · see citing works
Hellmann, M. D., Nathanson, T., Rizvi, H., Creelan, B. C., Sanchez-Vega, F., Ahuja, A., Ni, A., Novik, J. B., Mangarin, L. M. B., Abu-Akeel, M., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.018 · Cited by 1,095 · see citing works
Robbins, P. F., Lu, Y., El‐Gamil, M., Li, Y. F., Gross, C. A., Gartner, J. J., Lin, J., Teer, J. K., Cliften, P. F., Tycksen, E., et al. (2013) · Nature Medicine · doi:10.1038/nm.3161 · Cited by 1,074 · see citing works
Improved methods for predicting peptide binding affinity to MHC class II molecules
Jensen, K. K., Andreatta, M., Marcatili, P., Buus, S., Greenbaum, J., Zhen, Y., Sette, A., Peters, B., & Nielsen, M. (2018) · Immunology · doi:10.1111/imm.12889 · Cited by 805 · see citing works
Bennett, S. R. M., Carbone, F., Karamalis, F., Miller, J. F. A. P., & Heath, W. R. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.1.65 · Cited by 725 · see citing works
Linnemann, C., van Buuren, M. M., Bies, L., Verdegaal, E. M. E., Schotte, R., Calis, J. J. A., Behjati, S., Velds, A., Hilkmann, H., Atmioui, D. E., et al. (2014) · Nature Medicine · doi:10.1038/nm.3773 · Cited by 671 · see citing works
OSSENDORP, F. A., Mengedé, E., Camps, M. G. M., Filius, R., & Melief, C. J. M. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.187.5.693 · Cited by 609 · see citing works
Expression of tumour-specific antigens underlies cancer immunoediting
DuPage, M. J. P., Mazumdar, C., Schmidt, L., Cheung, A. F., & Jacks, T. (2012) · Nature · doi:10.1038/nature10803 · Cited by 529 · see citing works
Self-citationImmunology of Experimental Tumors
Old, L. J., & Boyse, E. A. (1964) · Annual Review of Medicine · doi:10.1146/annurev.me.15.020164.001123 · Cited by 498 · see citing works
Primary Antitumor Immune Response Mediated by CD4+ T Cells
Corthay, A., Skovseth, D. K., Lundin, K. U., Røsjø, E., Omholt, H., Hofgaard, P. O., Haraldsen, G., & Bogen, B. (2005) · Immunity · doi:10.1016/j.immuni.2005.02.003 · Cited by 478 · see citing works
The response of autologous T cells to a human melanoma is dominated by mutated neoantigens
Lennerz, V., Fatho, M., Gentilini, C., Frye, R. A., Lifke, A., Ferel, D., Wölfel, C., Huber, C., & Wölfel, T. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500090102 · Cited by 458 · see citing works
Bos, R., & Sherman, L. A. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1322 · Cited by 445 · see citing works
Targeting of cancer neoantigens with donor-derived T cell receptor repertoires
Strønen, E., Toebes, M., Kelderman, S., van Buuren, M. M., Yang, W., van Rooij, N., Donia, M., Böschen, M.-L., Lund‐Johansen, F., Olweus, J., et al. (2016) · Science · doi:10.1126/science.aaf2288 · Cited by 443 · see citing works
Spranger, S., Luke, J. J., Bao, R., Zha, Y., Hernandez, K. M., Yan, L., Gajewski, A. P., Andrade, J., & Gajewski, T. F. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1609376113 · Cited by 399 · see citing works
Tumor-Specific CD4+ T Cells Have a Major “Post-Licensing” Role in CTL Mediated Anti-Tumor Immunity
Marzo, A. L., Kinnear, B. F., Lake, R., et al. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.11.6047 · Cited by 334 · see citing works
Wong, S. B. J., Bos, R., & Sherman, L. A. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.5.3122 · Cited by 144 · see citing works
Patterns of protein-fold usage in eight microbial genomes: A comprehensive structural census
Gerstein, M. (1998) · Proteins Structure Function and Bioinformatics · doi:10.1002/(sici)1097-0134(19981201)33:4 · Cited by 114 · see citing works
An automated benchmarking platform for MHC class II binding prediction methods
Andreatta, M., Trolle, T., Zhen, Y., et al. (2017) · Bioinformatics · doi:10.1093/bioinformatics/btx820 · Cited by 95 · see citing works
Biochemical Large-Scale Identification of MHC Class I Ligands
Kowalewski, D. J., & Stevanović, S. (2012) · Methods in molecular biology · doi:10.1007/978-1-62703-218-6_12 · Cited by 76 · see citing works
Tungatt, K., Bianchi, V., Crowther, M. D., Powell, W. E., Schauenburg, A. J. A., Trimby, A., Donia, M., Miles, J. J., Holland, C. J., Cole, D. K., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401785 · Cited by 60 · see citing works
Corthay, A., Lundin, K. U., Lorvik, K. B., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4816 · Cited by 56 · see citing works
Suri, A., Walters, J. J., Rohrs, H. W., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.6.3849 · Cited by 56 · see citing works
CD4+ T Cell Help Selectively Enhances High-Avidity Tumor Antigen-Specific CD8+ T Cells
Zhu, Z., Cuss, S. M., Singh, V., et al. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1401571 · Cited by 43 · see citing works
Tumor-Unrelated CD4 T Cell Help Augments CD134 plus CD137 Dual Costimulation Tumor Therapy
Mittal, P., Rose, M. S., Wang, X., Ryan, J. M., Wasser, J. S., Vella, A. T., & Adler, A. J. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1502032 · Cited by 23 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [33]Gubin MM High-Dimensional Analysis Delineates Myeloid and Lymphoid Compartment Remodeling during Successful Immune-Checkpoint Cancer Therapy. Cell 175, 1443 (2018). 30445041 PMC6541402
- [38]Welch LR Hidden Markov Models and the Baum-Welch Algorithm. IEEE Inf. Theory Soc. Newsl 53, 10– 13 (2003).
Cited by
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A guide to cancer immunotherapy: from T cell basic science to clinical practice
Waldman, A. D., Fritz, J. M., & Lenardo, M. J. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0306-5 · Cited by 4,154 · see citing works
Saxena, M., van der Burg, S. H., Melief, C. J. M., & Bhardwaj, N. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00346-0 · Cited by 1,581 · see citing works
The Next Decade of Immune Checkpoint Therapy
Sharma, P., Siddiqui, B. A., Anandhan, S., Yadav, S. S., Subudhi, S. K., Gao, J., Goswami, S., & Allison, J. P. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1680 · Cited by 750 · see citing works
Ott, P. A., Hu-Lieskovan, S., Chmielowski, B., Govindan, R., Naing, A., Bhardwaj, N., Margolin, K., Awad, M. M., Hellmann, M. D., Lin, J. J., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.053 · Cited by 738 · see citing works
TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy
Molgora, M., Esaulova, E., Vermi, W., Hou, J., Chen, Y., Luo, J., Brioschi, S., Bugatti, M., Omodei, A. S., Ricci, B., et al. (2020) · Cell · doi:10.1016/j.cell.2020.07.013 · Cited by 656 · see citing works
“Since these tumors were developed in immunocompetent WT mice, their immunogenic profiles were edited by the immune system, and hence, they grow unopposed when transplanted into naive syngeneic WT hosts (Alspach et al., 2019; Schreiber et al., 2011; Shankaran et al., 2001).”
Self-citationcDC1 prime and are licensed by CD4(+) T cells to induce anti-tumour immunity
Ferris, S. T., Durai, V., Wu, R., Theisen, D. J., Ward, J. P., Bern, M. D., Davidson, J. T., Bagadia, P., Liu, T., Briseño, C. G., et al. (2020) · Nature · doi:10.1038/s41586-020-2611-3 · Cited by 611 · see citing works
Wells, D. K., van Buuren, M. M., Dang, K. K., Hubbard-Lucey, V. M., Sheehan, K. C. F., Campbell, K. M., Lamb, A., Ward, J. P., Sidney, J., Blazquez, A. B., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.015 · Cited by 538 · see citing works
Self-citationCytotoxic CD4+ T cells in cancer: Expanding the immune effector toolbox
Oh, D. Y., & Fong, L. (2021) · Immunity · doi:10.1016/j.immuni.2021.11.015 · Cited by 467 · see citing works
Identification of bacteria-derived HLA-bound peptides in melanoma
Kalaora, S., Nagler, A., Nejman, D., Alon, M., Barbolin, C., Barnea, E., Ketelaars, S. L. C., Cheng, K., Vervier, K., Shental, N., et al. (2021) · Nature · doi:10.1038/s41586-021-03368-8 · Cited by 457 · see citing works
Ricciuti, B., Arbour, K. C., Lin, J. J., Vajdi, A., Vokes, N., Hong, L., Zhang, J., Tolstorukov, M. Y., Li, Y. Y., Spurr, L. F., et al. (2022) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2021.10.013 · Cited by 394 · see citing works
Baessler, A., & Vignali, D. A. A. (2024) · Annual Review of Immunology · doi:10.1146/annurev-immunol-090222-110914 · Cited by 420 · see citing works
Freed-Pastor, W. A., Lambert, L. J., Ely, Z. A., Pattada, N. B., Bhutkar, A., Eng, G., Mercer, K. L., Garcia, A. P., Lin, L., Rideout, W. M., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.07.007 · Cited by 273 · see citing works
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Mondello, P., Tadros, S., Teater, M., Fontan, L., Chang, A. Y., Jain, N., Yang, H., Singh, S., Ying, H.-Y., Chu, C.-S., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0116 · Cited by 167 · see citing works
Yi, R., Hong, S., Zhang, Y., Lin, A., Ying, H., Zou, W., Wang, Q., Wei, T., Cheng, Q., Zhu, W., et al. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.757137 · Cited by 37 · see citing works
Bissonnette, R. P., Cesario, R. M., Goodenow, B., Shojaei, F., & Gillings, M. (2021) · BMC Cancer · doi:10.1186/s12885-021-08702-x · Cited by 24 · see citing works
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Kilian, M., Friedrich, M., Sanghvi, K., Green, E., Pusch, S., Kawauchi, D., Löwer, M., Sonner, J. K., Krämer, C., Zaman, J., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-1881 · Cited by 18 · see citing works
- Authors
- Alspach, E., Lussier, D. M., Miceli, A. P., Kizhvatov, I., DuPage, M., Luoma, A. M., Meng, W., Lichti, C. F., Esaulova, E., Vomund, A. N., Runci, D., Ward, J. P., Gubin, M. M., Medrano, R. F. V., Arthur, C. D., White, J. M., Sheehan, K. C. F., Chen, A., Wucherpfennig, K. W., Jacks, T., Unanue, E. R., Artyomov, M. N., & Schreiber, R. D.
- Affiliations
- Washington University in St. Louis (US)
- Koch Institute for Integrative Cancer Research At MIT (US)
- Dana-Farber Cancer Institute (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Schreiber, Robert D.
- ORCID
- Alspach, Elise
- Lussier, Danielle M.
- DuPage, Michel
- Luoma, Adrienne M.
- Meng, Wei
- Lichti, Cheryl F.
- Esaulova, Ekaterina
- Vomund, Anthony N.
- Ward, Jeffrey P.
- Gubin, Matthew M.
- Medrano, Ruan F. V.
- Arthur, Cora D.
- White, J. Michael
- Sheehan, Kathleen C. F.
- Chen, Alex
- Wucherpfennig, Kai W.
- Jacks, Tyler
- Unanue, Emil R.
- Artyomov, Maxim N.
- Schreiber, Robert D.
- Venue
- Nature
- Published
- 2019-10-23
- Volume
- 574
- Issue
- 7780
- Pages
- 696-701
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6858572
- OpenAlex
- W2982049472
- Cited by
- 846
- References
- 40
- Citations by year
- 2026: 80 · 2025: 108 · 2024: 126 · 2023: 127 · 2022: 143 · 2021: 142 · 2020: 113 · 2019: 6
- FWCI
- 41.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- RePEc: Research Papers in Economics (submittedVersion)
- PMC
- Funders
- Howard Hughes Medical Institute
- American Association for Cancer Research
- Cancer Research Institute
- Prostate Cancer Foundation
- Amgen
- Bristol-Myers Squibb
- Parker Institute for Cancer Immunotherapy
- Constellation Pharmaceuticals
- Jounce Therapeutics
- NGM Biopharmaceuticals
- National Institutes of Health
- Stand Up To Cancer
- National Cancer Institute (RO1CA190700, T32CA207021, R01CA190700, T32CA009547, R01CA238039, P30CA014051, P30CA091842, K12CA167540)
- National Institute of General Medical Sciences (T32GM007287)
- National Institute of Allergy and Infectious Diseases (R01AI114551)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-058177, R01DK058177)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- neoantigens, MHC class II, MHC class I, CD4+ T cells, CD8+ T cells, cancer immunotherapy, immune checkpoint inhibitors, tumor immunogenicity, tumor microenvironment, tumor rejection, immunogenicity, immunotherapy selection
- MeSH terms
- Animals, Histocompatibility Antigens Class II, Antigens, Neoplasm, Humans, Immunotherapy, Neoplasms, Experimental, Histocompatibility Antigens Class I, CD8-Positive T-Lymphocytes, Mice
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