Intercellular Communication and Cancer
ABOUT
The iCan research group at the i3S institute focuses on unraveling the complex communication networks within the tumor microenvironment that drive cancer development, metastasis, and resistance to therapy. Tumors are dynamic systems where cancerous and non-cancerous cells interact with the immune system and surrounding tissue, influencing every stage of cancer progression. The group’s core objective is to understand how intercellular communication shapes the behavior of cancer cells, impacts the immune response, and contributes to therapy resistance. By studying mechanisms such as extracellular vesicle-mediated signaling, cell-ECM interactions, and immune cell modulation, the group aims to identify novel therapeutic targets that can disrupt these communication networks. This holistic approach seeks to translate basic research into clinically relevant strategies, advancing the understanding and treatment of various cancer types.
RESEARCH
The iCan group leverages expertise in tumor immunology, cell-ECM interactions, leukemia microenvironments, and extracellular vesicles to offer a comprehensive approach to understanding and treating cancer. The group’s multidisciplinary research efforts aim to uncover new therapeutic avenues and improve the efficacy of cancer treatments across a variety of tumor types.
Cell-ECM Interactions and Cancer Invasion
Joana Figueiredo’s research investigates the role of E-cadherin mutations in modulating the interplay between cancer cells and the extracellular matrix (ECM). Her team has identified Integrin β1 as a critical factor in promoting abnormal cell-ECM interactions and driving cancer invasion, particularly in gastric cancer. Figueiredo’s work also highlights the role of ECM components, such as laminin γ2, in supporting cancer cell survival and motility, providing new insights into tumor aggressiveness.
Tumor Immunology and Therapy Resistance
The team led by José Carlos Machado focuses on understanding how cancer cells evade immune surveillance and develop resistance to therapies. His research explores the intricate communication between cancer and immune cells, demonstrating how molecular profiles of cancer cells are manipulated to suppress immune responses. Machado’s team is also uncovering the role of intercellular communication in promoting resistance by transferring resistance traits between cancer cells. These findings challenge traditional models of therapy resistance and point toward new therapeutic targets that disrupt intercellular communication in the tumor microenvironment.
Extracellular Vesicles and Pancreatic Cancer
Sónia Melo's team explores the role of extracellular vesicles (EVs) in pancreatic cancer, particularly how EVs are used by cancer cells to reprogram the tumor microenvironment. Her group focus on identifying the molecular cargo within these vesicles and determine how they influence tumor progression and resistance to therapy. By understanding the mechanisms of EVs-mediated communication, Melo’s team aims to develop novel therapeutic strategies to disrupt these pathways and improve patient outcomes.
Leukemia and Lymphoma Microenvironment
Nuno R. dos Santos' team focuses on the molecular and cellular mechanisms that promote leukemia and lymphoma, particularly the role of the thymic microenvironment in T-cell leukemia. His research delves into how leukemic cells manipulate the microenvironment to support disease progression and evade immune responses. He is also investigating new immunotherapeutic strategies, such as targeting the PSGL-1 checkpoint to enhance immune activity against lymphoma.

Team
Selected Publications
Extracellular Vesicles from Pancreatic Cancer Stem Cells Lead an Intratumor Communication Network (EVNet) to fuel tumour progression. Gut71(10):2043-2068, 2022. [Journal: Article] [CI: 59] [IF: 24,5]
DOI: 10.1136/gutjnl-2021-324994 SCOPUS: 85130807227
Costa e Silva M., Sucena I., Cirnes L., Machado J.C., Campainha S., Barroso A.
KIF5B-MET fusion variant in non-small cell lung cancer. Pulmonology28(4):315-316, 2022. [Journal: Letter] [CI: 2] [IF: 11,7]
DOI: 10.1016/j.pulmoe.2022.02.001 SCOPUS: 85131442502
Malfertheiner P., Megraud F., Rokkas T., Gisbert J.P., Liou J.M., Schulz C., Gasbarrini A., Hunt R.H., Leja M., O’Morain C., Rugge M., Suerbaum S., Tilg H., Sugano K., El-Omar E.M., Agreus L., Bazzoli F., Bordin D., Loginov A.S., Mario F.D., Dinis-Ribeiro M., Engstrand L., Fallone C., Goh K.L., Graham D., Kuipers E.J., Kupcinskas J., Lanas A., Machado J.C., Mahachai V., Marshall B.J., Milosavljevic T., Moss S.F., Park J.Y., Niv Y., Rajilic-Stojanovic M., Ristimaki A., Smith S., Tepes B., Wu C.Y., Zhou L.
Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut71(9):1724-1762, 2022. [Journal: Article] [CI: 628] [IF: 24,5]
DOI: 10.1136/gutjnl-2022-327745 SCOPUS: 85137345984
Freitas J.A., Gullo I., Garcia D., Miranda S., Spaans L., Pinho L., Reis J., Sousa F., Baptista M., Resende C., Leitão D., Durães C., Costa J.L., Carneiro F., Machado J.C.
The adaptive immune landscape of the colorectal adenoma–carcinoma sequence. International Journal of Molecular Sciences22(18):, 2021. [Journal: Article] [CI: 4] [IF: 6,2]
DOI: 10.3390/ijms22189791 SCOPUS: 85114644531
Adem B., Vieira P.F., Melo S.A.
Decoding the Biology of Exosomes in Metastasis. Trends in Cancer6(1):20-30, 2020. [Journal: Review] [CI: 44] [IF: 14,2]
DOI: 10.1016/j.trecan.2019.11.007 SCOPUS: 85076252541
Marques J.F., Junqueira-Neto S., Pinheiro J., Machado J.C., Costa J.L.
Induction of apoptosis increases sensitivity to detect cancer mutations in plasma. European Journal of Cancer127:130-138, 2020. [Journal: Article] [CI: 11] [IF: 9,2]
DOI: 10.1016/j.ejca.2019.12.023 SCOPUS: 85078673234
Fernandes M.G.O., Jacob M., Martins N., Moura C.S., Guimarães S., Reis J.P., Justino A., Pina M.J., Cirnes L., Sousa C., Pinto J., Marques J.A., Machado J.C., Hespanhol V., Costa J.L.
Targeted gene next-generation sequencing panel in patients with advanced lung adenocarcinoma: Paving the way for clinical implementation. Cancers11(9):, 2019. [Journal: Article] [CI: 25] [IF: 6,1]
DOI: 10.3390/cancers11091229 SCOPUS: 85071868403
Vaughn C.P., Costa J.L., Feilotter H.E., Petraroli R., Bagai V., Rachiglio A.M., Marino F.Z., Tops B., Kurth H.M., Sakai K., Mafficini A., Bastien R.R.L., Reiman A., Le Corre D., Boag A., Crocker S., Bihl M., Hirschmann A., Scarpa A., Machado J.C., Blons H., Sheils O., Bramlett K., Ligtenberg M.J.L., Cree I.A., Normanno N., Nishio K., Laurent-Puig P.
Simultaneous detection of lung fusions using a multiplex RT-PCR next generation sequencing-based approach: A multi-institutional research study. BMC Cancer18(1):, 2018. [Journal: Article] [CI: 23] [IF: 2,9]
DOI: 10.1186/s12885-018-4736-4 SCOPUS: 85051742631
Kamerkar S., Lebleu V.S., Sugimoto H., Yang S., Ruivo C.F., Melo S.A., Lee J.J., Kalluri R.
Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature546(7659):498-503, 2017. [Journal: Article] [CI: 1896] [IF: 41,6]
DOI: 10.1038/nature22341 SCOPUS: 85021081225
Yang S., Che S., Kurywchak P., Tavormina J., Gansmo L., Correa de Sampaio P., Tachezy M., Bockhorn M., Gebauer F., Haltom A., Melo S., LeBleu V., Kalluri R.
Detection of mutant KRAS and TP53 DNA in circulating exosomes from healthy individuals and patients with pancreatic cancer. Cancer Biology and Therapy18(3):158-165, 2017. [Journal: Article] [CI: 195] [IF: 3,4]
DOI: 10.1080/15384047.2017.1281499 SCOPUS: 85013638276