Unraveling spontaneous humoral immune responses against human cancer: a road to novel immunotherapies.

In immuno-oncology, the focus has traditionally been on αβ T cells, and immune checkpoint inhibitors that primarily target PD-1 or CTLA4 in these lymphocytes have revolutionized the management of multiple human malignancies. However, recent research highlights the crucial role of B cells and the antibodies they produce in antagonizing malignant progression, offering new avenues for immunotherapy. Our group has demonstrated that dimeric Immunoglobulin A can penetrate tumor cells, neutralize oncogenic drivers in endosomes, and expel them from the cytosol.

Presence of SARS-CoV-2-specific T cells before vaccination in the Mexican population.

The immune response to SARS-CoV-2 has been extensively studied following the pandemic outbreak in 2020; however, the presence of specific T cells against SARS-CoV-2 before vaccination has not been evaluated in Mexico. In this study, we estimated the frequency of T CD4+ and T CD8+ cells that exhibit a specific response to S (spike) and N (nucleocapsid) proteins in a Mexican population. We collected 78 peripheral blood samples from unvaccinated subjects, and the presence of antibodies against spike (RBD) and N protein was determined.

Harnessing γδ T Cells against Human Gynecologic Cancers.

Immuno-oncology has traditionally focused on conventional MHC-restricted αβ T cells. Yet, unconventional γδ T cells, which kill tumor cells in an MHC-unrestricted manner, display characteristics of effector activity and stemness without exhaustion and are nearly universally observed in human gynecologic malignancies, correlating with improved outcomes. These cells do not have a clear counterpart in mice but are also found in the healthy female reproductive tract.

Targeting intracellular oncoproteins with dimeric IgA promotes expulsion from the cytoplasm and immune-mediated control of epithelial cancers.

Dimeric IgA (dIgA) can move through cells via the IgA/IgM polymeric immunoglobulin receptor (PIGR), which is expressed mainly on mucosal epithelia. Here, we studied the ability of dIgA to target commonly mutated cytoplasmic oncodrivers. Mutation-specific dIgA, but not IgG, neutralized KRAS within ovarian carcinoma cells and expelled this oncodriver from tumor cells.

Beyond the antibody: B cells as a target for bacterial infection.

It is well established that B cells play an important role during infections beyond antibody production. B cells produce cytokines and are APCs for T cells. Recently, it has become clear that several pathogenic bacterial genera, such as Salmonella, Brucella, Mycobacterium, Listeria, Francisella, Moraxella, and Helicobacter, have evolved mechanisms such as micropinocytosis induction, inflammasome down-regulation, inhibitory molecule expression, apoptosis induction, and anti-inflammatory cytokine secretion to manipulate B cell functions influencing immune responses.