Independent Study Research Article Flashcards
In patients with metastatic melanoma, what percent (approx) of patients does high dose IL-2 induce durable immune responses?
5%
Why are many patients excluded as potential candidates for high dose IL-2 therapy?
due to the toxicity profile of IL-2
patients with melanoma, were treated with CTLA-4 blockage. In what (approx) of patients did CTLA-4 blockade induce durable objective tumor responses?
10%
The following are receptors on T cell. Name the counter molecules on dendritic cell
T cell: ICOS, CTLA-4,PD-1,CD28,CD40L
ICOS---ICOSL CTLA-4/CD154 ----CD86 PD-1 ----PDL1/L2 CD28---CD80 CD 40L----CD 40
What was the objective response in patients with advanced melanoma following treatment with monoclonal antibodies targeting PD-1/PDL-1?
The objective responses in patients with advanced melanoma in phase I trials occurred in about one third of patients, and the majority of these responses lasted
at least 1 year, with many of them ongoing at the time of
the initial data analysis
In a phase III trial with tremelimumab (anti CTLA4) the median response duration was approx how many times as long as the response duration with chemotherapy.
in the phase III trial, the median response
duration was almost three times as long as the response
duration with chemotherapy (35.8 vs. 13.7 months, P ¼
0.0011; refs. 21, 22).
CTLA-4 and PD-1 modulate different aspects of the T cell response: Explain how they differ
A, CTLA-4 is upregulated after antigen-specific activation of a naïve or memory T cell in lymphatic tissue, leading to decreased effector function (early activation phase).
B, PD-1 is mainly expressed on antigen experienced
memory T cells in peripheral tissues cells
When a TAA is presented in the T cell dependent area of a lymph node to its specific naive T cell (center), two signals are required to activate the T cell. name the two signals. What is the consequence of signal 3?
When a TAA is presented in the T-cell–dependent area of a lymph node to its specific naïve T cell (center), the latter requires signal 1 (antigen presentation to the
TCR) and 2 (costimulation) for full activation.
However, in the lymph node, T-cell activation is
interrupted when signal 3, mediated through interaction between CTLA-4 and CD80/86, takes over CD28 and CD80/86 interaction. This occurs 24 to 48
hours after the initiation of T-cell priming
In a B16 melanoma model, how did blockage of CTLA-4 and PD-1 influence TILS?
combined blockade with CTLA-4, PD-1, and PD-L1
blocking antibodies acts synergistically in a B16 melanoma
model. Importantly, in this model, inhibition of
CTLA-4 leads to a higher proportion of tumor-infiltrating
cells (TIL) expressing PD-1, whereas PD-1 blockade leads
to upregulation of CTLA-4 on TIL
