Translational Immunology Program (TRIMM)

The program joins together 13 active research groups in different career phases (10 PIs and 4 junior associate PIs) and is complemented with 8 clinical research teams led by the clinical researchers.
Our vision

Immunology is one of the most rapidly developing fields of medical science. Increasing understanding of the regulation of immune responses has led to the launch of several new therapeutic agents for clinical use, especially in cancer. However, not all cancer patients are responding to current immunological treatments and no cure or prevention is available for autoimmune diseases.

The ambitious goal of TRIMM is to explore the development and regulation of T cells and immune tolerance and understand the aberrant immune responses in auto- and alloimmune diseases and cancer. Our ultimate goal is to translate the discoveries into prevention, novel disease classifications, diagnostic tools, and personalized treatment.

Our main objectives are:

O1: Explore the development and regulation of T cells and immune tolerance

O2: Understand the aberrant immune responses in auto- and alloimmune diseases and cancer

O3: Translate the discoveries into prevention, novel disease classifications, diagnostic tools, and personalized treatment

Program director

Satu Mustjoki
Hematology Research Unit
Biomedicum Helsinki 1
Haartmaninkatu 8
P.O. Box 63
FI-00014 University of Helsinki
Tel: +358 9 471 71898
satu.mustjoki@helsinki.fi

  • Micaela Hernberg 
  • Hanna Jarva 
  • Kaija-Leena Kolho 
  • Karl Lemström 
  • Kimmo Porkka 
  • Tuula Salo 
  • Mikko Seppänen 
  • Taina Sipponen 
Key pub­lic­a­tions from TRIMM

T-cell biology/basic immunology

Hetemäki I, Saari V, Yohannes DA, Holopainen E, Holster T, Jokiranta S, Mäyränpää MI, Virtanen S, Mäkitie O, Kekäläinen E, Laakso S. Increased type 1 inflammation in gynecological cervicovaginal samples in patients with APS-1. J Allergy Clin Immunol. (2024) 

Hetemäki I, Sarkkinen J, Heikkilä N, Drechsel K, Mäyränpää MI, Färkkilä A, Laakso S, Mäkitie O, Arstila TP, Kekäläinen E. Dysregulated germinal center reaction with expanded T follicular helper cells in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy lymph nodes. J Allergy Clin Immunol. (2023) 

Sarkkinen, J., Dunkel, J., Tuulasvaara, A., Huuskonen, A., Atula, S., Kekäläinen, E. & Laakso, S.M. Ectopic germinal centers in the thymus accurately predict prognosis of myasthenia gravis after thymectomy. Mod Pathol 35, 1168-1174 (2022).

Heikkilä, N., Hetemäki, I., Sormunen, S., Isoniemi, H., Kekäläinen, E., Saramäki, J. & Arstila, T.P. Peripheral differentiation patterns of human T cells. Eur J Immunol 52, 882-894 (2022).

Meri, S., Bunjes, D., Cofiell, R. & Jodele, S. The Role of Complement in HSCT-TMA: Basic Science to Clinical Practice. Adv Ther 39, 3896-3915 (2022).

Lokki, A.I., Teirilä, L., Triebwasser, M., Daly, E., Bhattacharjee, A., Uotila, L., Llort Asens, M., Kurki, M.I., Perola, M., Auro, K., Salmon, J.E., Daly, M., Atkinson, J.P., Laivuori, H., Fagerholm, S. & Meri, S. Dysfunction of complement receptors CR3 (CD11b/18) and CR4 (CD11c/18) in pre-eclampsia: a genetic and functional study. Bjog 128, 1282-1291 (2021).

Hetemäki, I., Kaustio, M., Kinnunen, M., Heikkilä, N., Keskitalo, S., Nowlan, K., Miettinen, S., Sarkkinen, J., Glumoff, V., Andersson, N., Kettunen, K., Vanhanen, R., Nurmi, K., Eklund, K.K., Dunkel, J., Mäyränpää, M.I., Schlums, H., Arstila, T.P., Kisand, K., Bryceson, Y.T., Peterson, P., Otava, U., Syrjänen, J., Saarela, J., Varjosalo, M. & Kekäläinen, E. Loss-of-function mutation in IKZF2 leads to immunodeficiency with dysregulated germinal center reactions and reduction of MAIT cells. Sci Immunol 6, eabe3454 (2021).

Vuorela, A., Freitag, T.L., Leskinen, K., Pessa, H., Härkönen, T., Stracenski, I., Kirjavainen, T., Olsen, P., Saarenpää-Heikkilä, O., Ilonen, J., Knip, M., Vaheri, A., Partinen, M., Saavalainen, P., Meri, S. & Vaarala, O. Enhanced influenza A H1N1 T cell epitope recognition and cross-reactivity to protein-O-mannosyltransferase 1 in Pandemrix-associated narcolepsy type 1. Nat Commun 12, 2283 (2021).

Heikkilä, N., Vanhanen, R., Yohannes, D.A., Kleino, I., Mattila, I.P., Saramäki, J. & Arstila, T.P. Human thymic T cell repertoire is imprinted with strong convergence to shared sequences. Mol Immunol 127, 112-123 (2020).

Livson, S., Jarva, H., Kalliala, I., Lokki, A.I., Heikkinen-Eloranta, J., Nieminen, P. & Meri, S. Activation of the Complement System in the Lower Genital Tract During Pregnancy and Delivery. Front Immunol 11, 563073 (2020).

Reichhardt, M.P., Lundin, K., Lokki, A.I., Recher, G., Vuoristo, S., Katayama, S., Tapanainen, J.S., Kere, J., Meri, S. & Tuuri, T. Complement in Human Pre-implantation Embryos: Attack and Defense. Front Immunol 10, 2234 (2019).

Bastard, P., Rosen, L.B., Zhang, Q., Michailidis, E., Hoffmann, H.H., Zhang, Y., Dorgham, K., Philippot, Q., Rosain, J., Béziat, V., Manry, J., Shaw, E., Haljasmägi, L., Peterson, P., Lorenzo, L., Bizien, L., Trouillet-Assant, S., Dobbs, K., de Jesus, A.A., Belot, A., Kallaste, A., Catherinot, E., Tandjaoui-Lambiotte, Y., Le Pen, J., Kerner, G., Bigio, B., Seeleuthner, Y., Yang, R., Bolze, A., Spaan, A.N., Delmonte, O.M., Abers, M.S., Aiuti, A., Casari, G., Lampasona, V., Piemonti, L., Ciceri, F., Bilguvar, K., Lifton, R.P., Vasse, M., Smadja, D.M., Migaud, M., Hadjadj, J., Terrier, B., Duffy, D., Quintana-Murci, L., van de Beek, D., Roussel, L., Vinh, D.C., Tangye, S.G., Haerynck, F., Dalmau, D., Martinez-Picado, J., Brodin, P., Nussenzweig, M.C., Boisson-Dupuis, S., Rodríguez-Gallego, C., Vogt, G., Mogensen, T.H., Oler, A.J., Gu, J., Burbelo, P.D., Cohen, J.I., Biondi, A., Bettini, L.R., D'Angio, M., Bonfanti, P., Rossignol, P., Mayaux, J., Rieux-Laucat, F., Husebye, E.S., Fusco, F., Ursini, M.V., Imberti, L., Sottini, A., Paghera, S., Quiros-Roldan, E., Rossi, C., Castagnoli, R., Montagna, D., Licari, A., Marseglia, G.L., Duval, X., Ghosn, J., Tsang, J.S., Goldbach-Mansky, R., Kisand, K., Lionakis, M.S., Puel, A., Zhang, S.Y., Holland, S.M., Gorochov, G., Jouanguy, E., Rice, C.M., Cobat, A., Notarangelo, L.D., Abel, L., Su, H.C. & Casanova, J.L. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science 370 (2020).

Blauwendraat, C., Reed, X., Krohn, L., Heilbron, K., Bandres-Ciga, S., Tan, M., Gibbs, J.R., Hernandez, D.G., Kumaran, R., Langston, R., Bonet-Ponce, L., Alcalay, R.N., Hassin-Baer, S., Greenbaum, L., Iwaki, H., Leonard, H.L., Grenn, F.P., Ruskey, J.A., Sabir, M., Ahmed, S., Makarious, M.B., Pihlstrøm, L., Toft, M., van Hilten, J.J., Marinus, J., Schulte, C., Brockmann, K., Sharma, M., Siitonen, A., Majamaa, K., Eerola-Rautio, J., Tienari, P.J., Pantelyat, A., Hillis, A.E., Dawson, T.M., Rosenthal, L.S., Albert, M.S., Resnick, S.M., Ferrucci, L., Morris, C.M., Pletnikova, O., Troncoso, J., Grosset, D., Lesage, S., Corvol, J.C., Brice, A., Noyce, A.J., Masliah, E., Wood, N., Hardy, J., Shulman, L.M., Jankovic, J., Shulman, J.M., Heutink, P., Gasser, T., Cannon, P., Scholz, S.W., Morris, H., Cookson, M.R., Nalls, M.A., Gan-Or, Z. & Singleton, A.B. Genetic modifiers of risk and age at onset in GBA associated Parkinson's disease and Lewy body dementia. Brain 143, 234-248 (2020).

Raunio, A., Kaivola, K., Tuimala, J., Kero, M., Oinas, M., Polvikoski, T., Paetau, A., Tienari, P.J. & Myllykangas, L. Lewy-related pathology exhibits two anatomically and genetically distinct progression patterns: a population-based study of Finns aged 85. Acta Neuropathol 138, 771-782 (2019).

 

Allo- and autoimmunity

Tuovinen, E.A., Pöysti, S., Hamdan, F., Le, K.M., Keskitalo, S., Turunen, T., Minier, L., Mamia, N., Heiskanen, K., Varjosalo, M., Cerullo, V., Kere, J., Seppänen, M.R.J., Hänninen, A. & Grönholm, J. Characterization of Expanded Gamma Delta T Cells from Atypical X-SCID Patient Reveals Preserved Function and IL2RG-Mediated Signaling. J Clin Immunol (2022).

Huuhtanen, J., Bhattacharya, D., Lönnberg, T., Kankainen, M., Kerr, C., Theodoropoulos, J., Rajala, H., Gurnari, C., Kasanen, T., Braun, T., Teramo, A., Zambello, R., Herling, M., Ishida, F., Kawakami, T., Salmi, M., Loughran, T., Maciejewski, J.P., Lähdesmäki, H., Kelkka, T. & Mustjoki, S. Single-cell characterization of leukemic and non-leukemic immune repertoires in CD8(+) T-cell large granular lymphocytic leukemia. Nat Commun 13, 1981 (2022).

Tuovinen, E.A., Kuismin, O., Soikkonen, L., Martelius, T., Kaustio, M., Hämäläinen, S., Viskari, H., Syrjänen, J., Wartiovaara-Kautto, U., Eklund, K.K., Saarela, J., Varjosalo, M., Kere, J., Hautala, T. & Seppänen, M.R.J. Long-term follow up of families with pathogenic NFKB1 variants reveals incomplete penetrance and frequent inflammatory sequelae. Clin Immunol 246, 109181 (2022).

Johansson, T., Partanen, J. & Saavalainen, P. HLA allele-specific expression: Methods, disease associations, and relevance in hematopoietic stem cell transplantation. Front Immunol 13, 1007425 (2022).

Mustjoki, S. & Young, N.S. Somatic Mutations in "Benign" Disease. N Engl J Med 384, 2039-2052 (2021).

Valori, M., Jansson, L. & Tienari, P.J. CD8+ cell somatic mutations in multiple sclerosis patients and controls-Enrichment of mutations in STAT3 and other genes implicated in hematological malignancies. PLoS One 16, e0261002 (2021).

Johansson, T., Koskela, S., Yohannes, D.A., Partanen, J. & Saavalainen, P. Targeted RNA-Based Oxford Nanopore Sequencing for Typing 12 Classical HLA Genes. Front Genet 12, 635601 (2021).

Freitag, T.L., Podojil, J.R., Pearson, R.M., Fokta, F.J., Sahl, C., Messing, M., Andersson, L.C., Leskinen, K., Saavalainen, P., Hoover, L.I., Huang, K., Phippard, D., Maleki, S., King, N.J.C., Shea, L.D., Miller, S.D., Meri, S.K. & Getts, D.R. Gliadin Nanoparticles Induce Immune Tolerance to Gliadin in Mouse Models of Celiac Disease. Gastroenterology 158, 1667-1681.e1612 (2020).

Tuovinen, E.A., Grönholm, J., Öhman, T., Pöysti, S., Toivonen, R., Kreutzman, A., Heiskanen, K., Trotta, L., Toiviainen-Salo, S., Routes, J.M., Verbsky, J., Mustjoki, S., Saarela, J., Kere, J., Varjosalo, M., Hänninen, A. & Seppänen, M.R.J. Novel Hemizygous IL2RG p.(Pro58Ser) Mutation Impairs IL-2 Receptor Complex Expression on Lymphocytes Causing X-Linked Combined Immunodeficiency. J Clin Immunol 40, 503-514 (2020).

Kim, D., Park, G., Huuhtanen, J., Lundgren, S., Khajuria, R.K., Hurtado, A.M., Muñoz-Calleja, C., Cardeñoso, L., Gómez-García de Soria, V., Chen-Liang, T.H., Eldfors, S., Ellonen, P., Hannula, S., Kankainen, M., Bruck, O., Kreutzman, A., Salmenniemi, U., Lönnberg, T., Jerez, A., Itälä-Remes, M., Myllymäki, M., Keränen, M.A.I. & Mustjoki, S. Somatic mTOR mutation in clonally expanded T lymphocytes associated with chronic graft versus host disease. Nat Commun 11, 2246 (2020).

Yohannes, D.A., de Kauwe, A., Kaukinen, K., Kurppa, K., Mäki, M., Anderson, R.P., Linnarsson, S., Greco, D. & Saavalainen, P. Effects of In Vivo Gluten Challenge on PBMC Gene Expression Profiles in Diet Treated Celiac Disease. Front Immunol 11, 594243 (2020).

Rajamäki, K., Keskitalo, S., Seppänen, M., Kuismin, O., Vähäsalo, P., Trotta, L., Väänänen, A., Glumoff, V., Keskitalo, P., Kaarteenaho, R., Jartti, A., Hautala, N., Jackson, P., Nordström, D.C., Saarela, J., Hautala, T., Eklund, K.K. & Varjosalo, M. Haploinsufficiency of A20 impairs protein-protein interactome and leads into caspase-8-dependent enhancement of NLRP3 inflammasome activation. RMD Open 4, e000740 (2018).

 

Cancer immunology

Feola S, Chiaro J, Fusciello M, Russo S, Kleino I, Ylösmäki L, Kekäläinen E, Hästbacka J, Pekkarinen PT, Ylösmäki E, Capone S, Folgori A, Raggioli A, Boni C, Tezzi C, Vecchi A, Gelzo M, Kared H, Nardin A, Fehlings M, Barban V, Ahokas P, Viitala T, Castaldo G, Pastore L, Porter P, Pesonen S, Cerullo V. PeptiVAX: A new adaptable peptides-delivery platform for development of CTL-based, SARS-CoV-2 vaccines. Int J Biol Macromol. (2024)

Feola, S., Chiaro, J., Martins, B., Russo, S., Fusciello, M., Ylösmäki, E., Bonini, C., Ruggiero, E., Hamdan, F., Feodoroff, M., Antignani, G., Viitala, T., Pesonen, S., Grönholm, M., Branca, R.M.M., Lehtiö, J. & Cerullo, V. A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines. Elife 11 (2022).

Huuhtanen, J., Chen, L., Jokinen, E., Kasanen, H., Lönnberg, T., Kreutzman, A., Peltola, K., Hernberg, M., Wang, C., Yee, C., Lähdesmäki, H., Davis, M.M. & Mustjoki, S. Evolution and modulation of antigen-specific T cell responses in melanoma patients. Nat Commun 13, 5988 (2022).

Kudling, T.V., Clubb, J.H.A., Quixabeira, D.C.A., Santos, J.M., Havunen, R., Kononov, A., Heiniö, C., Cervera-Carrascon, V., Pakola, S., Basnet, S., Grönberg-Vähä-Koskela, S., Arias, V., Gladwyn-Ng, I., Aro, K., Bäck, L., Räsänen, J., Ilonen, I., Borenius, K., Räsänen, M., Hemminki, O., Rannikko, A., Kanerva, A., Tapper, J. & Hemminki, A. Local delivery of interleukin 7 with an oncolytic adenovirus activates tumor-infiltrating lymphocytes and causes tumor regression. Oncoimmunology 11, 2096572 (2022).

Huuhtanen, J., Ilander, M., Yadav, B., Dufva, O.M., Lähteenmäki, H., Kasanen, T., Klievink, J., Olsson-Strömberg, U., Stentoft, J., Richter, J., Koskenvesa, P., Höglund, M., Söderlund, S., Dreimane, A., Porkka, K., Gedde-Dahl, T., Gjertsen, B.T., Stenke, L., Myhr-Eriksson, K., Markevärn, B., Lübking, A., Dimitrijevic, A., Udby, L., Bjerrum, O.W., Hjorth-Hansen, H. & Mustjoki, S. IFN-α with dasatinib broadens the immune repertoire in patients with chronic-phase chronic myeloid leukemia. J Clin Invest 132 (2022).

Feola, S., Haapala, M., Peltonen, K., Capasso, C., Martins, B., Antignani, G., Federico, A., Pietiäinen, V., Chiaro, J., Feodoroff, M., Russo, S., Rannikko, A., Fusciello, M., Koskela, S., Partanen, J., Hamdan, F., Tähkä, S.M., Ylösmäki, E., Greco, D., Grönholm, M., Kekarainen, T., Eshaghi, M., Gurvich, O.L., Ylä-Herttuala, S., RM, M.B., Lehtiö, J., Sikanen, T.M. & Cerullo, V. PeptiCHIP: A Microfluidic Platform for Tumor Antigen Landscape Identification. ACS Nano 15, 15992-16010 (2021).

Chiaro, J., Kasanen, H.H.E., Whalley, T., Capasso, C., Grönholm, M., Feola, S., Peltonen, K., Hamdan, F., Hernberg, M., Mäkelä, S., Karhapää, H., Brown, P.E., Martins, B., Fusciello, M., Ylösmäki, E.O., Greco, D., Kreutzman, A.S., Mustjoki, S., Szomolay, B. & Cerullo, V. Viral Molecular Mimicry Influences the Antitumor Immune Response in Murine and Human Melanoma. Cancer Immunol Res 9, 981-993 (2021).

Santos, J., Heiniö, C., Quixabeira, D., Zafar, S., Clubb, J., Pakola, S., Cervera-Carrascon, V., Havunen, R., Kanerva, A. & Hemminki, A. Systemic Delivery of Oncolytic Adenovirus to Tumors Using Tumor-Infiltrating Lymphocytes as Carriers. Cells 10 (2021).

Quixabeira, D.C.A., Zafar, S., Santos, J.M., Cervera-Carrascon, V., Havunen, R., Kudling, T.V., Basnet, S., Anttila, M., Kanerva, A. & Hemminki, A. Oncolytic Adenovirus Coding for a Variant Interleukin 2 (vIL-2) Cytokine Re-Programs the Tumor Microenvironment and Confers Enhanced Tumor Control. Front Immunol 12, 674400 (2021).

Ylösmäki, E., Fusciello, M., Martins, B., Feola, S., Hamdan, F., Chiaro, J., Ylösmäki, L., Vaughan, M.J., Viitala, T., Kulkarni, P.S. & Cerullo, V. Novel personalized cancer vaccine platform based on Bacillus Calmette-Guèrin. J Immunother Cancer 9 (2021).

Dufva, O., Pölönen, P., Brück, O., Keränen, M.A.I., Klievink, J., Mehtonen, J., Huuhtanen, J., Kumar, A., Malani, D., Siitonen, S., Kankainen, M., Ghimire, B., Lahtela, J., Mattila, P., Vähä-Koskela, M., Wennerberg, K., Granberg, K., Leivonen, S.K., Meriranta, L., Heckman, C., Leppä, S., Nykter, M., Lohi, O., Heinäniemi, M. & Mustjoki, S. Immunogenomic Landscape of Hematological Malignancies. Cancer Cell 38, 380-399.e313 (2020).

Fusciello, M., Fontana, F., Tähtinen, S., Capasso, C., Feola, S., Martins, B., Chiaro, J., Peltonen, K., Ylösmäki, L., Ylösmäki, E., Hamdan, F., Kari, O.K., Ndika, J., Alenius, H., Urtti, A., Hirvonen, J.T., Santos, H.A. & Cerullo, V. Artificially cloaked viral nanovaccine for cancer immunotherapy. Nat Commun 10, 5747 (2019).