ASH News Daily 2017 - Issue 3 - A-20

ASH News Daily

Page A-20

Monday, December 11, 2017

Immunology
«« From Page A-9

underlies many chronic diseases
and is a better predictor of mortality than telomere length or other senescence markers.
Dr. Sarah Gaffen discussed how
IL-17 and the subsets of T cells that
produce it coordinate immunity to
fungal infections. "Our model system is oral infection with Candida
albicans which causes oral thrush
(candidiasis). We have recently
identified a peptide secreted by C.
albicans, candidalysin, that triggers
cells to make IL-17. This peptide
induces tissue damage in the epithelial layer, and that damage then

causes IL-17 to be produced," she
said. C. albicans is usually a harmless commensal, but in individuals who are immunocompromised,
by chemotherapy or anti-rejection
agents, for example, it can be lifethreatening.
The converse of an effective immune response is that inflammatory cytokines can cause damage.
"They didn't evolve to do that.
They evolved to protect us from
infection. But on the flipside, some
of the signals that IL-17 triggers
can cause autoimmune pathology,
and so consequently drugs to target IL-17 have been developed, and
are still being developed. You need
enough IL-17 to keep infections like

C. albricans at bay, but too much is
pathogenic." Further understanding of how the oral epithelial cell
barrier interacts with pathogens
might one day inform the design of
antifungal vaccines.
Dr. Antonio Lanzavecchia discussed how analysis of human antibody responses can provide new
approaches for developing antiviral and antiparasitic prophylactic
and therapeutic antibodies and designing better vaccines.
Using cell culture-based, highthroughput cellular screening to
analyze the repertoires of immortalized human memory B cells and
cultured single plasma cells, Dr.
Lanzavecchia's group has discov-

American Society of Hematology
Helping hematologists conquer blood diseases worldwide

ered a new mechanism of antibody
diversity in response to malaria.
Screening a large number of donors in Kenya led to identification
of a few individuals producing
broadly-reacting antibodies to the
parasites. These broadly reacting
antibodies contained a leukocyte
associated immunoglobulin-like receptor 1 (LAIR1) exon between the
V and DJ domains and arise from a
single expanded clone.
Screening individuals exposed
to malaria in Tanzania and Mali indicate that about 10 percent have
LAIR1-containing antibodies. Other individuals show a new insertion
modality in the antibody switch
region. These antibodies also bind
to all malaria parasites. A few mutations can reduce binding to collagen. Differential splicing can lead
to antibodies with and without the
LAIR1 domain. Dr. Lanzavecchia
calls these antibodies "natural bispecific antibodies," noting that
"nature has made a human bispecific antibody before man."
Dr. Lederman indicated no relevant
conflicts of interest.

Blood Editor-in-Chief Search Announcement
The American Society of Hematology is looking for its next Editor-inChief for the Blood Journal.
Candidates must have appreciation for the broad and comprehensive
knowledge of basic research and clinical investigation in hematology
and its subspecialty areas, a distinguished research and publication
record, high standing among peers, and demonstrated editing,
writing, and reviewing skills. The Blood Editor-in-Chief serves for five
years beginning January 1, 2020.
All members of ASH are encouraged to submit a letter of intent
if they are interested in the position or nominate the name of a
potential candidate. Candidates are also asked to submit their CV
and a vision statement of no more than 2,000 words.

For a detailed position
description and application
requirements, please visit:

bloodjournal.org/eic
Applications must be received on
or before February 28, 2018.

Lymphoma
«« From Page A-10

evaluating BCL2 inhibitors, antiCD38 antibodies, and anti-CXCR4
antibodies will pave the way towards a more personalized approach on the treatment of WM."
Dr. Thieblemont was the final
presenter with a focus on splenic
and nodal marginal zone lymphoma. She described unique features
in the biology of these conditions,
such as the strongly biased IGHV
repertoire in each disorder, which
suggests a significant pathogenic
contribution from antigen stimulation. Clinical developments for
both entities have recently been oriented by genomic studies that demonstrate overlapping mutational
profiles featuring enriched signaling pathways such as NOTCH and
BcR/TLR/NF-KB. She also reviewed the current management
for these two conditions, where
there is no clear standard and therapeutic strategies are rapidly evolving. Several treatment approaches
including B cell signaling modifiers
like ibrunitinib and copanlisib as
well as combination therapy using
lenalidomide with rituximab have
shown promising efficacy. Dr. Thieblemont did, however, underscore
the challenges posed by the relative
rarity of these conditions in conducting prospective clinical trials.
Dr. Forsberg and Dr. Shah indicated
no relevant conflicts of interest.

http://www.bloodjournal.org/eic

Table of Contents for the Digital Edition of ASH News Daily 2017 - Issue 3