ABOUT

Tumors are composed of distinct subpopulations of cancer and non-cancer cells. Moreover, cancer cells invade, metastasize, and thrive in diverse niches in the host organism. These hallmarks of cancer reflect a high degree of plasticity of cancer cells and a systemic rather than a localized disease. Hence, understanding the communication network that connects all the cellular components of cancer provides a unique opportunity to translate basic research into clinically relevant information. The major goal of our research group is to understand the biological significance of communication among cells of the tumor microenvironment, and determine how it influences cancer onset, progression, and clinical response. Our current focus is on the role of communication:
1) established with the immune system in shaping the genetic and expression landscape of cancer cells; and
2) mediated by extracellular vesicles (EVs) in disease progression and acquisition of resistance to therapy..

RESEARCH

Our lab is interested in understanding how communication between cancer and immune cells triggers an immune response and allows escape from immunosurveillance. In a collaborative study, we have shown that the glycosylation profile of cancer cells is immunosuppressive and is a consequence of a selective effect of adaptive immunity (Cancer Immunol Res 8:1407-25, 2020). We have also found that there is a progressive loss of adaptive immune cells during the colorectal adenoma carcinoma sequence suggestive of a dysfunctional state of immune cell exhaustion that likely results from persistent antigen stimulation and chronic inflammation.

We identified for the first time an organized network of communication centered in EVs originated in cancer stem cells and demonstrated its significance in the biology of the tumor. This communication is a fundamental process for cooperation within the tumor and contributes to its plastic nature and resistance to therapy. In a collaborative study, we have demonstrated that exosomes can be used as delivery vehicles for therapies that target specific mutations in cancer cells (Nature 546:498-503, 2017).

We are also testing the hypothesis that mutation-driven resistance to therapy is transferred from therapy-resistant to therapy-sensitive cancer cells. We have data showing that intercellular communication, either EV-mediated or through cell-free molecules, plays a key role in the process. Our results question the established concept that acquisition of resistance to targeted therapies relies solely on the selection of tumor cells carrying a specific resistance mutation, which is then passed on to its progeny through cell division.