Immune phenotypes and checkpoint molecule expression of clonally expanded lymph node-infiltrating T cells in classical Hodgkin lymphoma.
Alexej BallhausenAmin Ben HamzaCarlotta WeltersKerstin DietzeLars BullingerHans-Peter RahnSylvia HartmannMartin-Leo HansmannLeo HansmannPublished in: Cancer immunology, immunotherapy : CII (2022)
Lymph node-infiltrating T cells have been of particular interest in classical Hodgkin lymphoma (cHL). High rates of complete therapeutic responses to antibody-mediated immune checkpoint blockade, even in relapsed/refractory patients, suggest the existence of a T cell-dominated, antigen-experienced, functionally inhibited and lymphoma-directed immune microenvironment. We asked whether clonally expanded T cells (1) were detectable in cHL lymph nodes, (2) showed characteristic immune phenotypes, and (3) were inhibited by immune checkpoint molecule expression. We applied high-dimensional FACS index sorting and single cell T cell receptor αβ sequencing to lymph node-infiltrating T cells from 10 treatment-naïve patients. T cells were predominantly CD4 + and showed memory differentiation. Expression of classical immune checkpoint molecules (CTLA-4, PD-1, TIM-3) was generally low (< 12.0% of T cells) and not different between CD4 + and CD8 + T cells. Degrees of clonal T cell expansion varied between patients (range: 1-18 expanded clones per patient) and was almost exclusively restricted to CD8 + T cells. Clonally expanded T cells showed non-naïve phenotypes and low checkpoint molecule expression similar to non-expanded T cells. Our data suggest that the therapeutic effects of immune checkpoint blockade require mechanisms in addition to dis-inhibition of pre-existing lymphoma-directed T cell responses. Future studies on immune checkpoint blockade-associated effects will identify molecular T cell targets, address dynamic aspects of cell compositions over time, and extend their focus beyond lymph node-infiltrating T cells.
Keyphrases
- lymph node
- hodgkin lymphoma
- end stage renal disease
- single cell
- poor prognosis
- ejection fraction
- chronic kidney disease
- neoadjuvant chemotherapy
- newly diagnosed
- prognostic factors
- diffuse large b cell lymphoma
- binding protein
- patient reported outcomes
- acute lymphoblastic leukemia
- electronic health record
- case report
- artificial intelligence
- cell therapy
- high throughput
- bone marrow
- oxidative stress
- combination therapy
- multiple myeloma
- rectal cancer