Alvaro López Malizia

@inbirs.org.ar

INSTITUTE OF BIOMEDICAL RESEARCH IN RETROVIRUS AND AIDS (INBIRS)

Alvaro López Malizia


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https://researchid.co/alvaroresearhid

RESEARCH, TEACHING, or OTHER INTERESTS

Immunology and Allergy, Molecular Biology, Molecular Medicine, Cancer Research
3

Scopus Publications

94

Scholar Citations

4

Scholar h-index

4

Scholar i10-index

Scopus Publications

  • Platelets modulate CD4+ T-cell function in COVID-19 through a PD-L1 dependent mechanism
    Ana Paletta, Facundo Di Diego García, Augusto Varese, Fernando Erra Diaz, Julián García, et al.
    British Journal of Haematology, 2022
    SummarySevere COVID‐19 is associated with a systemic inflammatory response and progressive CD4+ T‐cell lymphopenia and dysfunction. We evaluated whether platelets might contribute to CD4+ T‐cell dysfunction in COVID‐19. We observed a high frequency of CD4+ T cell–platelet aggregates in COVID‐19 inpatients that inversely correlated with lymphocyte counts. Platelets from COVID‐19 inpatients but not from healthy donors (HD) inhibited the upregulation of CD25 expression and tumour necrosis factor (TNF)‐α production by CD4+ T cells. In addition, interferon (IFN)‐γ production was increased by platelets from HD but not from COVID‐19 inpatients. A high expression of PD‐L1 was found in platelets from COVID‐19 patients to be inversely correlated with IFN‐γ production by activated CD4+ T cells cocultured with platelets. We also found that a PD‐L1‐blocking antibody significantly restored platelets’ ability to stimulate IFN‐γ production by CD4+ T cells. Our study suggests that platelets might contribute to disease progression in COVID‐19 not only by promoting thrombotic and inflammatory events, but also by affecting CD4+ T cells functionality.
  • Aberrant fucosylation enables breast cancer clusterin to interact with dendritic cell-specific ICAM-grabbing non-integrin (DC-SIGN)
    Antonela Merlotti, Alvaro López Malizia, Paula Michea, Pierre-Emmanuel Bonte, Christel Goudot, et al.
    Oncoimmunology, 2019
    Clusterin is a glycoprotein able to mediate different physiological functions such as control of complement activation, promotion of unfolded protein clearance and modulation of cell survival. Clusterin is overexpressed in many types of cancers and a large body of evidence suggests that it promotes carcinogenesis and tumor progression. We have previously described a novel clusterin glycoform present in human semen, but not in serum, highly enriched in terminal fucose motifs. Here we show that human luminal breast cancer (LBC) clusterin also bears terminal fucosylated glycans, conferring clusterin the ability to interact with DC-SIGN, a C-type lectin receptor expressed by myeloid cells. This clusterin glycosylation pattern was absent or diminished in non-involved juxtatumoral tissue, suggesting that fucosylated clusterin might represent a cancer associated glycoform. We also found that DC-SIGN is expressed by luminal breast cancer intratumoral macrophages. Moreover, experiments performed in vitro using semen fucosylated clusterin and monocyte derived macrophages showed that the interaction of semen clusterin with DC-SIGN promoted a proangiogenic profile, characterized by a high production of VEGF, IL-8 and TNF-α. Our results reveal an unexpected complexity on the structure and function of secretory clusterin produced by tumors and suggest that fucosylated clusterin produced by luminal breast cancer cells might play a role in tumor progression by promoting the release of pro-angiogenic factors by intratumoral macrophages.
  • Prostaglandin E2 Antagonizes TGF-β actions during the differentiation of monocytes into dendritic cells
    Federico Remes Lenicov, Ana Luz Paletta, Melina Gonzalez Prinz, Augusto Varese, Clara E. Pavillet, et al.
    Frontiers in Immunology, 2018
    Inflammatory dendritic cells (DCs) are a distinct subset of DCs that derive from circulating monocytes infiltrating injured tissues. Monocytes can differentiate into DCs with different functional signatures, depending on the presence of environment stimuli. Among these stimuli, transforming growth factor-beta (TGF-β) and prostaglandin E2 (PGE2) have been shown to modulate the differentiation of monocytes into DCs with different phenotypes and functional profiles. In fact, both mediators lead to contrasting outcomes regarding the production of inflammatory and anti-inflammatory cytokines. Previously, we have shown that human semen, which contains high concentrations of PGE2, promoted the differentiation of DCs into a tolerogenic profile through a mechanism dependent on signaling by E-prostanoid receptors 2 and 4. Notably, this effect was induced despite the huge concentration of TGF-β present in semen, suggesting that PGE2 overrides the influence exerted by TGF-β. No previous studies have analyzed the joint actions induced by PGE2 and TGF-β on the function of monocytes or DCs. Here, we analyzed the phenotype and functional profile of monocyte-derived DCs differentiated in the presence of TGF-β and PGE2. DC differentiation guided by TGF-β alone enhanced the expression of CD1a and abrogated LPS-induced expression of IL-10, while differentiation in the presence of PGE2 impaired CD1a expression, preserved CD14 expression, abrogated IL-12 and IL-23 production, stimulated IL-10 production, and promoted the expansion of FoxP3+ regulatory T cells in a mixed lymphocyte reaction. Interestingly, DCs differentiated in the presence of TGF-β and PGE2 showed a phenotype and functional profile closely resembling those induced by PGE2 alone. Finally, we found that PGE2 inhibited TGF-β signaling through an action exerted by EP2 and EP4 receptors coupled to cyclic AMP increase and protein kinase A activity. These results indicate that PGE2 suppresses the influence exerted by TGF-β during DC differentiation, imprinting a tolerogenic signature. High concentrations of TGF-β and PGE2 are usually found in infectious, autoimmune, and neoplastic diseases. Our observations suggest that in these scenarios PGE2 might play a mandatory role in the acquisition of a regulatory profile by DCs.

RECENT SCHOLAR PUBLICATIONS

  • Unsupervised spatial decomposition of Lymphoma subtypes reveals distinct biological programs via MEFISTO
    AL Malizia, M Chatziaslani, M Sibai, D Grases, M Pérez, G Ferrer, ...
    MDPI , 2025
    2025
  • Deciphering the spatial architecture of Lymphoma
    M Chatziaslani, AL Malizia, M Al Sibai, D Grases, E Pérez, G Ferrer, ...
    MDPI , 2025
    2025
  • Clusterin protects mature dendritic cells from reactive oxygen species mediated cell death
    A López Malizia, A Merlotti, PE Bonte, M Sager, Y Arribas De Sandoval, ...
    Oncoimmunology 13 (1), 2294564 , 2024
    2024
    Citations: 11
  • Immunological variables and tumor types influence one-year survival probability in cancer patients: A comprehensive analysis using logistic regression and decision tree models
    AL Malizia
    medRxiv, 2023.10. 25.23297566 , 2023
    2023
  • Platelets modulate CD4 + T‐cell function in COVID‐19 through a PD‐L1 dependent mechanism
    A Paletta, F Di Diego Garcia, A Varese, F Erra Diaz, J Garcia, JC Cisneros, ...
    British journal of haematology 197 (3), 283-292 , 2022
    2022
    Citations: 18
  • Survival of Mature Dendritic Cells Dependent on Clusterin Expression
    RA Mendoza, AL Malizia, GA Garcia, JA Sabattê
    The FASEB Journal 34 (S1), 1-1 , 2020
    2020
  • Platelets-monocytes aggregates in COVID19 pathogenesis
    AL Paletta, F Di Diego García, J García, JC Cisneros, A Varese, ...
    Fundación Revista Medicina , 2020
    2020
  • B. abortus down modulates inflammation in monocytes/macrophages through mTOR activation
    AP Melnyczajko, AI Pesce Viglietti, PC Arriola Benitez, MV Gentilini, ...
    Fundación Revista Medicina , 2020
    2020
  • Aberrant fucosylation enables breast cancer clusterin to interact with dendritic cell-specific ICAM-grabbing non-integrin (DC-SIGN)
    A Merlotti, AL Malizia, P Michea, PE Bonte, C Goudot, MS Carregal, ...
    Oncoimmunology 8 (9), e1629257 , 2019
    2019
    Citations: 33
  • Prostaglandin E2 antagonizes TGF-β actions during the differentiation of monocytes into dendritic cells
    F Remes Lenicov, AL Paletta, M Gonzalez Prinz, A Varese, CE Pavillet, ...
    Frontiers in Immunology 9, 1441 , 2018
    2018
    Citations: 32

MOST CITED SCHOLAR PUBLICATIONS

  • Aberrant fucosylation enables breast cancer clusterin to interact with dendritic cell-specific ICAM-grabbing non-integrin (DC-SIGN)
    A Merlotti, AL Malizia, P Michea, PE Bonte, C Goudot, MS Carregal, ...
    Oncoimmunology 8 (9), e1629257 , 2019
    2019
    Citations: 33
  • Prostaglandin E2 antagonizes TGF-β actions during the differentiation of monocytes into dendritic cells
    F Remes Lenicov, AL Paletta, M Gonzalez Prinz, A Varese, CE Pavillet, ...
    Frontiers in Immunology 9, 1441 , 2018
    2018
    Citations: 32
  • Platelets modulate CD4 + T‐cell function in COVID‐19 through a PD‐L1 dependent mechanism
    A Paletta, F Di Diego Garcia, A Varese, F Erra Diaz, J Garcia, JC Cisneros, ...
    British journal of haematology 197 (3), 283-292 , 2022
    2022
    Citations: 18
  • Clusterin protects mature dendritic cells from reactive oxygen species mediated cell death
    A López Malizia, A Merlotti, PE Bonte, M Sager, Y Arribas De Sandoval, ...
    Oncoimmunology 13 (1), 2294564 , 2024
    2024
    Citations: 11
  • Unsupervised spatial decomposition of Lymphoma subtypes reveals distinct biological programs via MEFISTO
    AL Malizia, M Chatziaslani, M Sibai, D Grases, M Pérez, G Ferrer, ...
    MDPI , 2025
    2025
  • Deciphering the spatial architecture of Lymphoma
    M Chatziaslani, AL Malizia, M Al Sibai, D Grases, E Pérez, G Ferrer, ...
    MDPI , 2025
    2025
  • Immunological variables and tumor types influence one-year survival probability in cancer patients: A comprehensive analysis using logistic regression and decision tree models
    AL Malizia
    medRxiv, 2023.10. 25.23297566 , 2023
    2023
  • Survival of Mature Dendritic Cells Dependent on Clusterin Expression
    RA Mendoza, AL Malizia, GA Garcia, JA Sabattê
    The FASEB Journal 34 (S1), 1-1 , 2020
    2020
  • Platelets-monocytes aggregates in COVID19 pathogenesis
    AL Paletta, F Di Diego García, J García, JC Cisneros, A Varese, ...
    Fundación Revista Medicina , 2020
    2020
  • B. abortus down modulates inflammation in monocytes/macrophages through mTOR activation
    AP Melnyczajko, AI Pesce Viglietti, PC Arriola Benitez, MV Gentilini, ...
    Fundación Revista Medicina , 2020
    2020