A complex cross talk between tumor cells and the tumor microenvironment, comprising tumor-infiltrating lymphocytes, dictates the clinical outcome in neoplastic diseases. The unit is interested in defining cells and molecules relevant in the differentiation of CD4+ T lymphocyte subsets with anti-tumor or tumor-promoting function. The information derived by these studies will help in the design of clinical protocols of immune- biotherapy in neoplastic patients.
Group studies are focused on pancreatic cancer and multiple myeloma and they are conducted in collaboration with surgeons, clinical oncologists and pathologists of the Institute. In particular, specific aims are:
- evaluating tumor infiltrating Th cell subsets and defining possible correlation between the features of the Th subsets identified and the clinical outcome (i.e., predictive markers);
- studying cells and mechanisms dictating Th polarization;
- studying how the different Th cell subsets exert pro- versus anti-tumor activity in these pathologies.
De Monte L, Wörmann S, Brunetto E, Heltai S, Magliacane G, Reni M, Paganoni AM, Recalde H, Mondino A, Falconi M, Aleotti F, Balzano G, Algül H, Doglioni C, Protti MP. Basophil recruitment into tumor-draining lymph nodes correlates with Th2 inflammation and reduced survival in pancreatic cancer patients. Cancer Res. 2016 Apr 1;76(7):1792-803.
Wörmann SM, Song L, Ai J, Diakopoulos KN, Kurkowski MU, Görgülü K, Ruess D, Campbell A, Doglioni C, Jodrell D, Neesse A, Demir IE, Karpathaki AP, Barenboim M, Hagemann T, Rose-John S, Sansom O, Schmid RM, Protti MP, Lesina M, Algül H. Loss of P53 function activates JAK2-STAT3 signaling to promote pancreatic tumor growth, stroma modification, and gemcitabine resistance in mice and is associated with patient survival. Gastroenterology. 2016 Jul;151(1):180-193.e12.
Di Lullo G, Marcatti M, Heltai S, Brunetto E, Tresoldi C, Bondanza A, Bonini C, Ponzoni M, Tonon G, Ciceri F, Bordignon C, Protti MP. Th22 cells increase in poor prognosis multiple myeloma and promote tumor cell growth and survival. Oncoimmunology. 2015 Feb 3;4(5):e1005460.
De Monte L, Reni M, Tassi E, Clavenna D, Papa I, Recalde H, Braga M, Di Carlo V, Doglioni C, Protti MP. Intratumor T helper type 2 cell infiltrate correlates with cancer- associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer. J Exp Med. 2011 Mar 14;208(3):469-78.
Tassi E, Braga M, Longhi R, Gavazzi F, Parmiani G, Di Carlo V, Protti MP. Non- redundant role for IL-12 and IL-27 in modulating Th2 polarization of carcinoembryonic antigen specific CD4 T cells from pancreatic cancer patients. PLoS One. 2009 Oct 2;4(10):e7234.
Tassi E, Gavazzi F, Albarello L, Senyukov V, Longhi R, Dellabona P, Doglioni C, Braga M, Di Carlo V, Protti MP. Carcinoembryonic antigen-specific but not antiviral CD4+ T cell immunity is impaired in pancreatic carcinoma patients. J Immunol. 2008 Nov 1;181(9):6595-603.
Seresini S, Origoni M, Lillo F, Caputo L, Paganoni AM, Vantini S, Longhi R, Taccagni G, Ferrari A, Doglioni C, Secchi P, Protti MP. IFN-gamma produced by human papilloma virus-18 E6-specific CD4+ T cells predicts the clinical outcome after surgery in patients with high-grade cervical lesions. J Immunol. 2007 Nov 15;179(10):7176-83.
Consogno G, Manici S, Facchinetti V, Bachi A, Hammer J, Conti-Fine BM, Rugarli C, Traversari C, Protti MP. Identification of immunodominant regions among promiscuous HLA-DR-restricted CD4+ T-cell epitopes on the tumor antigen MAGE-3. Blood. 2003 Feb 1;101(3):1038-44.
Sturniolo T, Bono E, Ding J, Raddrizzani L, Tuereci O, Sahin U, Braxenthaler M, Gallazzi F, Protti MP, Sinigaglia F, Hammer J. Generation of tissue-specific and promiscuous HLA ligand databases using DNA microarrays and virtual HLA class II matrices. Nat Biotechnol. 1999 Jun;17(6):555-61.
Manici S, Sturniolo T, Imro MA, Hammer J, Sinigaglia F, Noppen C, Spagnoli G, Mazzi B, Bellone M, Dellabona P, Protti MP. Melanoma cells present a MAGE-3 epitope to CD4(+) cytotoxic T cells in association with histocompatibility leukocyte antigen DR11. J Exp Med. 1999 Mar 1;189(5):871-6.