>> WELL, PEOPLE ARE STILL
DRAFTING IN -- DRIFTING IN BUT
I THINK IT'S TIME TO GET
STARTED. I'M BOB, AND IT'S
REALLY WITH GREAT PLEASURE THAT
I ANNOUNCE AND INTRODUCE ROMNEY
WHO IS A FELLOW IN THE
MALIGNANCY BRANCH AND SHE'S
GOING TO TALK ABOUT KA POE SI
SAR ROMA AND HER TALK IS CALLED
HIDDEN IN PLAIN SITE. KA POE SI
SARCOMA AND OTHER
KSHV-ASSOCIATED DISORDERS
SHE DID HER TRAINING IN ENGLAND
AND DID HER UNDERGRADUATE IN
MEDICAL SCHOOL AND POSTGRADUATE
TRAINING THERE IN THE IMPERIAL
COLLEGE, ROYAL COLLEGE OF
PHYSICIANS, INSTITUTE OF CANCER
AND ALSO DID POSTGRADUATE
TRAINING IN MEDICAL ONCOLOGY IN
VARIOUS TEACHING HOSPITALS IN
LONDON. DURING THIS PERIOD IN
2014 SHE ALSO GOT A MASTER'S OF
PUBLIC HEALTH FROM COLUMBIA
UNIVERSITY. IN 2016 SHE CAME
ACROSS THE POND TO BOSTON AND
WORKED FOR A YEAR AS AN
EDITORIAL FELLOW IN THE NEW
ENGLAND JOURNAL WORKING WITH DAN
LON GO I THINK MANY OF YOU KNOW
HERE AND SHE JOINED THE BRANCH
IN 2017. SHE CAME AS AN
ASSISTANT RESEARCH PHYSICIAN
THEN SHE WAS AN ACI AND BECAME A
SCHOLAR THIS PAST FALL. SHE'S
HAD A NUMBER OF AWARDS INCLUDING
THE IMPERIAL COLLEGE OF MEDICINE
COLORS AND THAT'S WITH A U. THE
FEDERAL TECHNOLOGY TRANSFER
AWARDS AND THE NCI DIRECTOR
AWARD FOR DEI INITIATIVES. SHE
IS A GOOD CITIZEN AND SERVES ON
A NUMBER OF COMMITTEES INCLUDING
THE NIH CDC GUIDELINES FOR
OPPORTUNISTIC INFECTIONS.
WHICH HAS NATIONAL IMPLICATIONS.
THE INTERNATIONAL KSH ADVISORY
COMMITTEE AND ALSO SERVES ON A
NUMBER OF COMMITTEES HERE IN THE
NIH INCLUDING THE SAFETY
MONITORING COMMITTEE, THE BIO
THERAPY COMMITTEE AND THE CANCER
HEALTH DISPARITIES HEALTH
COMMITTEE IN WHICH SHE'S BEEN
THE CO-CHAIR SINCE 2021. HER
RESEARCH IS ON THOSE CANCER
CAUSED BY KSHV AND WITHOUT
FURTHER ADO I WILL TURN THE
PODIUM OVER TO THE DOCTOR.
PLEASE GIVE HER A GOOD WELCOME.
>> THANK YOU FOR THAT KIND
INTRODUCTION. IT'S A DELIGHT TO
BE HERE TODAY AND THANK YOU TO
ALL TUNING IN AS WELL. WITH THE
TITLE OF MY TALK IN KA POE SI
SARCOMA IN GENERAL I THOUGHT WE
WOULD START A LITTLE BIT IN THE
PAST SO WHEN IT IS DESCRIBED IN
THE 1800S IT WAS DEDOMINANTLY
SEEN IN OLDER MEDITERRANEAN MEN
AND IT WAS OBVIOUSLY VERY
SURPRISING TO THE MEDICAL
COMMUNITY AND THE ONCOLOGY
COMMUNITY TO SEE OUTBREAKS OF
THIS CONDITION AMONG YOUNG MEN
WHO HAD SEX WITH MEN AND DYING
FROM THIS DISEASE IN THE EARLY
80S. AND WHAT HAPPENED
SUBSEQUENT TO THAT IS THE
IDENTIFICATION OF A VIRUS, HIV,
THAT LED TO THE DEVELOPMENT OF
ANTIRETROVIRAL THERAPY FIRST IN
1987. THAT MANY INDIVIDUALS
HERE IN THIS INSTITUTION PLAYED
A ROLE IN THAT. BUT I ALSO WANT
TO TAKE A MOMENT TO RECOGNIZE
THE EFFORTS OF THE ADVOCACY
COMMUNITY TO ENSURE WIDESPREAD
DISSEMINATION OF THESE
MEDICATIONS. AND THIS IS WHERE
THE STORY DIVERGES BETWEEN HIV
AND KAPOSI SARCOMA TO SOME
DEGREE. AT THE TIME IT WAS
UNCLEAR HOW THIS INITIAL
HARBINGER OF HIV WAS ACTUALLY
TRANSMITTED. WAS IT A VIRUS?
WAS IT A SEXUALLY TRANSMITTED
DISEASE? AND IT WAS ONLY IN
1994 THAT CHANG AND MOORE
DESCRIBED THIS VIRUS, YOU WILL
HEAR ME REFER TO IT AS KSHV AND
THIS VIRUS WAS ASSOCIATED WITH
KS BUT ALSO WAS FOUND TO BE
ASSOCIATED AND CAUSATIVE FOR
OTHER ENTITIES SUCH AS PRIMARY
EFFUSION LYMPHOMA AROUND THIS
TIME THE DEVELOPMENT OF
ANTIRETROVIRAL THERAPY WAS MUCH
MORE SIGNIFICANT WITH
COMBINATIONS AVAILABLE FOR
PATIENTS AND THEN FURTHER
THERAPIES WERE DEVELOPED IN THE
EARLY PART OF THE 90S, DESPITE
COMBINATION ANTIRETROVIRAL
THERAPY WE CONTINUED TO SEE HIGH
LEVELS OF KAPOSI SARCOMA AND
PEOPLE DYING OF THIS DISEASE.
WE THEN RECOGNIZED THIS WAS A
GLOBAL ISSUE AND IN 2003 THE
FUNDING WAS IDENTIFIED TO ENSURE
THAT ANTIRETROVIRAL THERAPY WAS
AVAILABLE. THERE ARE ONLY THREE
CURRENT FDA APPROVED THERAPIES
FOR KS AND THE MOST RECENT ONE
WAS IN 2020 BASED ON WORK FROM
US. WITH REGARDS TO KSHV WE
KNOW THIS IS A DNA VIRUS, IT HAS
TWO PROGRAMS. ONE WHICH IS OF
LATENCY WHERE THE VIRUS IS ABLE
TO PERSIST AND EXIST IN ITS OWN
AND THE SECOND BEING PROGRAMS OF
LIDDIC REPLICATION. THE
INTERESTING THING ABOUT KSHV IS
IT'S ABILITY OF HOST PROCESSES.
TO EVADE THE HOST IMMUNE SYSTEM
AND APOPTOSIS. IT'S ABILITY TO
PROPAGATE ANGIOGENESIS, IT HAS
ITS OWN CELL CYCLE COMPONENTS.
AND IT ALSO HAS ITS OWN HOMOLOGS
OF CYTOKINES. WHAT WE NOW KNOW
ABOUT THIS VIRUS IS THAT IT IS
HIGHLY PREVALENT IN SUB-SAHARAN
AFRICA WHERE THERE ARE LIMITED
RESOURCES, WHEREAS IN THE UNITED
STATES, WE KNOW THAT IT'S
PREDOMINANTLY TRANSMITTED AMONG
THE MSM POPULATION. SO IN TERMS
OF THE DISEASE MANIFESTATION IF
WE PICK UP A TEXTBOOK ON THIS
VIRUS WE RECOGNIZE THERE ARE
FOUR PRINCIPLE CONDITIONS CAUSED
BY KSHV. FIRST IS KA POE POSI
SARCOMA SEEN ON THE SKIN AND IS
FROM INFECTION AND ALSO MANIFEST
IN THE GI TRACT OR IN THE LUNGS.
THE SECOND IS MULTICENTRIC
CASTLEMAN DISEASE AND THIS IS
A -- IT'S A PLASMA KNOW PLASTIC
FORM OF THIS DISEASE WHEN IT'S
AFFECTED BY KSHV SEEN
PREDOMINANTLY WITHIN PEOPLE WITH
HIV. PATIENTS CAN HAVE SYSTEMIC
SIDE EFFECTS. THERE'S A PET
SCAN WHERE YOU CAN SEE
WIDESPREAD LYMPHADENOPATHY AND
INCREASE IN ORGAN SIZES. THESE
PATIENTS CAN BE VERY UNWELL IF
THIS DISEASE IS NOT IDENTIFIED
PROMPTLY. THE THIRD DISEASE IS
A TYPE OF NON-HODGKIN LYMPHOMA
CALLED PRIMARY EFFUSION. WHERE
YOU CAN SEE THE FLUID BETWEEN
THE LUNG AND THE RIB SPACE.
PATIENTS CAN AGAIN, BE VERY
UNWELL WITH BREATHLESSLY. THIS
ASSOCI
ASSOCIATED CYTOKINE SYNDROME WAS
FOUND IN 2006 AND IT IS A
DIAGNOSIS OF EXCLUSION WHERE YOU
HAVE TO RULE OUT CASTLEMAN, MCD
O PEL. BUT AS THESE CONDITIONS
WE SEE IN THEIR ENTIRETY.
MCD, PEL AND KICS HAVE ELEVATED
VIRUS LEVELS IN THE BLOOD AND WE
SEE ALL OF THESE CONDITIONS
DESPITE EXCELLENT HIV CONTROL OR
HIGH CD4 COULDN'TS AS WELL.
AND FROM HERE ON YOU'LL HEAR ME
REFER TO MCD, PEL AND KICS AS
KEDS. WE RECOGNIZE THESE
DISEASES VERY WELL BUT THE
REALITY IS THEY OFTEN OCCUR AS
OVERLAPPING DISEASES AT THE SAME
TIME AND AT MY TIME HERE WORKING
AT THE BRANCH I REALIZED IT IS
AN OVERLAP. THIS ONE VIRUS
CAUSES NINE MANIFESTATIONS OF
THE DISEASE IN DIFFERENT
COMBINATIONS SO IN REALITY, WHAT
WE SEE IS A PATIENT WHO IS
SYSTEMICALLY UNWELL WITH
EVIDENCE OF SOME KS ON THEIR
SKIN CAN OFTEN BE LEFT WITH AN
UNDIAGNOSED UNDERLYING PROCESS
OFTEN ATTRIBUTED TO HIV. THIS
PATIENT, FOR EXAMPLE, THEY HAVE
IMAGING FINDINGS SUCH AS
INTERSTITIAL INFEW TRACTS ON
THEIR CT SCAN UP IN THE CORNER
HERE.
THEY MAY HAVE EFFUSIONS OR FLUID
IN THEIR LUNGS, THEY MAY ALSO
HAVE EVIDENCE OF ARROW THREE MA
OR READINESS IN THEIR SCOPES AS
WELL AS THE ENDOSCOPY OF THEIR
STOMACH DUE TO SYMPTOMS.
AND IT'S ONLY UNTIL AN EXPERT
THAT PATHOLOGIST IS THAT WE'RE
ABLE TO IDENTIFY MULTIPLE
CONDITIONS IN THE SAME PATIENT.
AS YOU CAN IMAGINE IF THEY WERE
ON THE OUTSIDE THEY MAY JUST BE
DIAGNOSED WITH SAR ROMA. IT
BECOMES COMPLICATED VERY
QUICKLY.
THE OTHER ISSUE IS THAT THESE
DISEASES AND THEIR
MANIFESTATIONS OF KEDS CAN BE
EXTREMELY RESOURCE INTENSIVE
OFTEN REQUIRING PATIENT TO HAVE
MULTIPLE BIOPSIES OF MULTIPLE
ORGANS IN ORDER TO LEAD TO A
DIAGNOSIS AND SO THIS INTENSIVE
ABILITY TO PROCEDURALIZE AND
DIAGNOSE OUR PATIENTS IS OFTEN
CHALLENGING IN RESOURCE
SETTINGS.
AND WHY IS THIS IMPORTANT?
BECAUSE IT DRIVES THE TREATMENT
DECISION. IF YOU HAVE SOMEONE
WITH KS WHO ACTUALLY HAS PEL OR
CASTLEMAN'S THAT IS ACTUALLY A
VERY DIFFERENT TREATMENT
PARADIGM FROM JUST HAVING KS
ALONE.
AND SO IF YOU DON'T DIAGNOSE
THESE KEDS APPROPRIATELY
PATIENTS WILL BE SIMPLY
DIAGNOSED WITH KS AND DIE FROM
THEIR DISEASE AND SO AN
APPROPRIATE DIAGNOSIS IS
PARAMOUNT SO I WOULD LIKE TO
TAKE YOU ALL TO THE THIRD FLOOR
IN OUR INTENSIVE CARE UNIT HERE
AT THE NCI AND THIS IS -- AT THE
NIH, AND THIS IS WHERE OUR FIRST
PROJECT STARTS. WE LOOKED BACK
AT THE 42 PATIENTS WITH KEDS ALL
OF WHOM HAD KD WITH ACTIVE
DISEASE. SO, AGAIN, REMIND
OURSELVES THAT ONE VIRUS CAUSES
NINE MANIFESTATIONS OF THESE
DISEASES. THESE WERE ALL
PATIENTS WHO HAD FEVERS, WHO
NEEDED INTENSIVE SUPPORT FOR
THEIR BREATHING, OR THEIR
CARDIOVASCULAR SYSTEM. THEY MAY
NEED SUPPORT FOR THEIR KIDNEYS.
AND THEY HAD THESE TENTATIVE
DIAGNOSES WHICH WE HAD MADE AS
EXPERTS IN THIS FIELD. AND WHAT
I WANT TO DRAW YOUR EYE TO IS
THE DIAGRAM OF DIAGNOSES THAT
WERE NOTED AT THE TIME OF
INITIAL ICU ADMISSION. WHAT WE
FIND IS AS A GROUP OF
PHYSICIANS, WE CONTINUED TO LOOK
FOR DISORDERS CAUSED BY KSHV
EVEN IN A CONDITION WHERE YOU
HAD TO EXCLUDE MCD OR PEL.
THESE WITH KS HAS KICS BEFORE
THEY WENT TO THE ICU BUT WE
CONTINUE TO LOOK IN THESE
PATIENTS AND WE IDENTIFY THAT
20% OF THESE INDIVIDUALS ENDED
UP WITH MCD, PEL OR A
COMBINATION OF THESE DISORDERS
SO, AGAIN, THAT TELLS YOU THAT
EVEN IN A PLACE LIKE THIS, EVEN
WITH THE EXPERTISE, MAKING THESE
DIAGNOSES ARE OFTEN EXTREMELY
CHALLENGING. AND SO THATS US TO
MY RESEARCH GOAL WHICH IS TO
DEFINE THESE PATIENTS WITH KEDS.
AND HOW THEY DIFFER FROM
PATIENTS WITH KS ALONE. AND
WITH THE LANDSCAPE IDENTIFYING
THE CELL TYPES AND THE PATHWAYS
THAT DRIVE THESE DIFFERENCES AND
WOE NEED TO DO THIS IN ORDER TO
DEVELOP BETTER OR -- SUPPORTIVE
DIAGNOSTIC TOOLS IN LIMITED
RESOURCE SETTINGS AND ALSO
CONSIDER NEW THERAPEUTIC
STRATEGIES FOR THESE DISORDERS.
SO HOW WE'D LIKE TO DO THAT
INITIALLY IS TO START WITH SOME
OF OUR COHORTS THAT ARE
HISTORICAL WITHIN THE THE HAM.
I WOULD LIKE TO DRAW YOUR
ATTENTION TO THESE THREE GRAPHS
THESE ARE INFLAMMATORY CYTOKINES
TAKEN THERE THE SERUM OF
PATIENTS AT THE TIME OF ACTIVE
DISEASE. I'D LIKE TO SHOW YOU
THAT CLEARLY WHEN YOU HAVE KS,
YOU HAVE A SLIGHTLY LOWER IN
INFLAMMATORY COMPILE COMPARED TO
SOMEONE WITH KICS AND ONCE YOU
START THE PROFILE IT'S SIMILAR
AMONG THESE GROUPS OFTEN. SO
YOU CAN SEE THOSE WITH KICS AS
COMPARED TO MCD OR PEL ARE
LARGELY SIMILAR WHEREAS IF YOU
HAVE KS YOUR INFLAMMATORY
PROFILE IS SLIGHTLY MORE MUTED.
AND THIS ACTUALLY TRANSLATES TO
OUTCOMES BECAUSE WHEN WE THINK
ABOUT THE -- WHEN YOU SEE THIS
CURVE WE'RE ABLE TO LOOK AT THE
SURVIVAL OUTCOMES WE SEE QUITE
QUICKLY IN THE TOP LINE OF
PATIENTS WITH KS ALONE THEY HAVE
A MUCH BETTER SURVIVAL AS
COMPARED TO HAVING AN
INFLAMMATORY CONDITION SUCH AS
MCD, KICS OR PEL. IT ASKS THE
QUESTION WE CLEARLY SEE
INFLAMMATION AS AN IMPORTANT
COMPONENT IN KEDS BUT IS IT A
DRIVER A BYSTANDER OR HOW CAN WE
THINK ABOUT THERAPIES WHEN WE
ADDRESS THESE INFLAMMATORY
PROFILES. OFTEN WHEN I GIVE
THESE TALKS I'M OFTEN ASKED YOU
SEE IL-6 ELEVATED IS THAT A
THERAPEUTIC TARGET AND IN OUR
BRAND WE HAVE LOOKED AT IL-6 AS
A THERAPEUTIC TARGET AND WE HAVE
STUDIED CASTLEMAN DISEASE WHERE
WE KNOW THERE'S ELEVATED IL-6 IN
THE BLOOD AS I JUST SHOWED YOU
AND WE USED THE RECEPTOR
INHIBITOR IN EIGHT PATIENTS WITH
HIV AND CASTLEMAN DISORDER.
CASTLEMAN DISEASE, TWO OF WHOM
ALSO HAD CONCURRENT KS. OF FIVE
OF THE EIGHT PATIENTS HAD A
RESPONSE IN THEIR CASTLEMAN'S
BUT THIS WAS OFTEN A TEMPORARY
RESPONSE. AND MOST OF THESE
PATIENTS ENDED UP HAVING
SUBSEQUENT WORSTENING OF THEIR
CASTLEMAN'S REQUIRING THE
STANDARD OF CARE WHICH IS A
B-CELL DEPLETING THERAPY CALLED
RETOX MAB. WE ASKED, WHY IS
THIS? WE HAVE CLEARLY SEEN IL-6
ELEVATED IN THE BLOOD WHY ARE WE
SEEING LACK OF RESPONSE AND THE
ANSWER TO THIS COMES FROM THE
VIRUS ITSELF. KSHV IS AVAILABLE
TO BYPASS THE IL-6 RECEPTOR SO
EVEN THOUGH WE'RE INHIBITING IT
IT IS STILL ABLE TO TRIGGER THE
DOWNSTREAM PROCESSES. SO I'D
LIKE TO TAKE A STEP FURTHER UP
AND THINK ABOUT THE UPSTREAM
PROCESSES FROM CYTOKINE
PRODUCTION AND TALK A LITTLE BIT
ABOUT THE APPLICATION. SO
UNDERSTANDING THE PATHWAYS OF
STREAM OF INFLAMMATION OF THESE
INFLAMMATORY CYTOKINES MAY HELP
US UNDERSTAND THE PATHOGENESIS
OF KEDS, HELP US IDENTIFY NEW
DIAGNOSTIC METHODS AND MAY ALSO
OFFER NEW THERAPEUTIC
OPPORTUNITIES. THE INFLAMMASOME
ITSELF CONTROLS THE RESPONSE AND
IMMUNE RESPONSE AGAINST
INFECTIOUS AGENTS AND LEADS TO
CELL DEATH. AND THIS IS KNOWN
TO BE -- IS NOTABLE IN SEVERAL
DISORDERS INCLUDING HIV AND
CANCER. AND I'D LIKE TO NOTE
THAT THE LAB HERE IN NIAD HAVE
BEEN LEADERS IN IDENTIFYING
ACTIVATION IN SEVERAL HIV
ASSOCIATED DISORDERS AND THOSE
ASSOCIATED WITH OPPORTUNISTIC
INFECTIONS IN THOSE WITH HIV.
SO I'D LIKE TO GO INTO A LITTLE
BIT OF THE DETAILS IN WHAT THE
INFLAMMASOME IS AND YOU CAN SEE
THAT IN THE FIGURE ON THE LEFT.
THE INFLAMMASOME CYTOKINE
REQUIRE THE INFLAMMASOME
ACTIVATION AND HOW THIS WORKS IS
IT REQUIRES THREE PRINCIPLE
COMPONENTS. THE FIRST IS A NOD
LIKE RECEPTOR THE SECOND IS THE
APOPTOSIS ASSOCIATED SPECK LIKE
PROTEIN CONTAINING A CARD SO
YOU'LL HEAR ME REFER TO THIS AS
ASC AND THEN THE SPACE ONE WHICH
IS THE MOST COMMON ACTIVATED
SPACE. SO IN THIS
COLLABORATION, WITH THE SIR
LETTY LAB WE LOOKED AT PATIENTS
WITH KED AND LOOKED AT THEIR
PERIPHERAL BLOOD SAMPLES DURING
A PERIOD OF ACTIVE DISEASE.
WE LOOKED AT THE ASC AGGREGATES
IN PARTICIPANT SAMPLES USING
IMAGE STREAM SPECIFICALLY
LOOKING AT MONOCYTES BY
SELECTING THE CD 14 POSITIVE
CELLS SO UPON TRIGGERING OF THE
INFLAMMASOME SENSORS THIS
RING-LIKE STRUCTURE WHICH IS AN
ASC SPECK AND A MARKER OF
CANONICAL ACTIVATION WAS
DETECTED BY FLUORESCENCE
MICROSCOPY, THIS EXPERIMENT DONE
THAT WERE PREINCUBATED CELLS WAS
FOLLOWED BY IMMUNO PHENOTYPING
AND INTRACELLULAR STAINING. SO
BY DOING THIS WE WERE ABLE TO
SCREEN FOR FLICKER POSITIVE ASC
AGGREGATES WITHIN BLOOD CELLS IN
ADDITION WE ALSO MEASURED THE
INFLAMMATORY CYTOKINES WHICH
INCLUDED IO 1 BETA AND HAD TWO
ADDITIONAL COMPARATOR GROUPS THE
FIRST BEING THOSE WHO ARE HIV
NEGATIVE VOLUNTEER OR HVS AND
THOSE WHO WERE PEOPLE WITH HIV
WITHOUT KEDS AT ALL SO
INTERESTINGLY THE INFLAMMASOME
ACTIVATION AS YOU CAN SEE BY THE
FLICKER WAS INCREASED IN THOSE
WITH KEDS AS COMPARED TO THOSE
WHO WERE HEALTHY VOLUNTEERS AND
IL-18 WAS ALSO INCREASED AS
COMPARED TO PEOPLE WITH HIV AND
HEALTHY VOLUNTEERS. IT WAS
NOTABLE THAT THOSE VOYINDIVIDUA
WHEN COMPARING THOSE WITH W KD
AND HIV THEY WERE ALMOST SIMILAR
TO THE DISEASE PROCESSES IN BOTH
GROUPS.
INTERESTINGLY WE ALSO NOTED THAT
FLICKER WAS CORRELATING WITH
KSHV AND WITH IL-6 AND 10
FURTHER INDICATING THE ROLE OF
THE VIRUS IN THIS PROCESS. WE
WERE ALSO ABLE TO DELINEATE IN
THIS PCA ALL THE MARKERS OF
INFLAMMASOME ACTIVATION IN
ADDITION TO THE INFLAMMATORY
BIOMARKERS AND WE SEE IN THE
VARIOUS COLORED GROUPS
SEPARATION OF KEDS THEMSELVES.
YOU CAN SEE THAT INDIVIDUALS
WITH PEL AND KS IN THE BLUE AND
GREEN RESPECTIVELY DO CLUSTER
TOGETHER WHEREAS THOSE WITH MCD
SEEM TO BE SOMEWHAT DIFFERENT.
PERHAPS IDENTIFYING DELINEATIONS
IN THE INFLAMMASOME ACTIVATION
PATHWAYS BETWEEN THESE DISEASES.
AS A FOLLOW UP TO THIS WORK,
WE'VE ALSO SEEN THAT IL-18 IS A
MARKER OF POTENTIAL DIAGNOSTIC
MARKER THAT CAN SEPARATE THIS
KED PROCESS AS COMPARED TO OTHER
OPPORTUNISTIC INFECTIONS IN
PEOPLE WITH HIV. SO THIS IS
WORK THAT WITHIN THE SIR LETTY
LAB THE DOCTOR WILL BE PURSUING
AS WE MOVE FORWARD.
SO SO FAR WHAT I'VE TAKEN YOU
THROUGH IS CLEAR EVIDENCE OF
INFLAMMATION IN THE SERUM. IN
OUR PBMCS WE'VE SEEN THE
INFLAMMASOME ACTIVATION, THAT
SEEMS TO BE DISTINCT BY KEDS.
IT SEEMS WE ARE VERY LUCKY IN
THE WORK THAT WE DO THAT WE ARE
ABLE TO ACCESS TUMORS FOR EASILY
BECAUSE FORTUNATELY AND
UNFORTUNATELY, THEY'RE ON THE
SKIN SO THE NATURAL QUESTION
BECOMES WHAT DO THE TUMORS
THEMSELVES TELL US AND THIS IS
WORK THAT I WAS VERY EXCITED TO
DO WITH MY COLLEAGUE, JOE IN THE
HAM, LOOKING AT PATIENTS WITH KS
BOTH ON THEIR SKIN AND IN THEIR
GI TRACT SO IN 22 KS SPECIMENS
WE LOOKED AT THOSE -- TEN
PATIENTS WHO JUST HAD SKIN AND
TWELVE OF WHOM HAD GI KS WE GOT
COMPARED BOTH NORMAL AND KS IN
BOTH SITES. AND THIS WAS BOTH
RNA SEQUENCING THAT WAS DONE.
THREE OF THE PATIENTS THAT HAD
SKIN AND GI KS. WE DID BULK RNA
SEQUENCING THAT ALSO INCLUDED
KSH VGS AND THERE WAS AN OVERLAP
OF 26 GENES BETWEEN THESE SITES
AND INTERESTINGLY WHEN WE LOOK
AT THESE 26 GENES THERE ARE TWO
THAT POP UP AS PARTICULARLY
INTERESTING SDC 1 WHICH IS A
GLYCOPROTEIN THAT REGULATES
FACTORS IN PEOPLE AND HAVE BEEN
A CONTRIBUTING TO CAR SIN KNOW
GENESIS AS DESCRIBED IN THE
LITERATURE.
FLIT FOUR HAS BEEN NOTED TO
REGULATE THE LYMPHATIC SYSTEM
AND TOGETHER THE DOCTOR'S GROUP
HAS DONE SOME VERY ELEGANT
EXPERIMENTING SHOWING THE ROLE
OF SDC ONE. AND I URGE YOU TO
READ OUR PAPER FROM LAST YEAR.
AMONG THESE PARTICIPANTS OF 19
AS I MENTIONED, 74 ACTUALLY HAD
CONCURRENT KEDS AND WHEN WE LOOK
ACROSS SKIN VERSUS -- SKIN KS
VERSUS NORMAL WE SEE THAT THERE
ARE INCREASED IL-6 LEVELS IN
THOSE KS LESIONS AS COMPARED TO
ADJACENT SKIN THAT'S NORMAL AND
THIS IS MORE TRUE AS COMPARED TO
GI KS WHICH IS PARTICULARLY
INTERESTING AND IN PATIENTS WHO
HAD SKIN KS AS COMPARED TO THEIR
NORMAL ADJACENT TISSUES THE IL-6
GENE EXPRESSION ACTUALLY
COORDINATED WITH THE GENE
EXPRESSION PROFILING MIMICKING
WHAT WE SEE IN THE CIRCULATION.
SO WHEN WE LOOK TO SEE, WELL,
CAN THE SKIN LESIONS OR THE GI
LESIONS GIVE US AN INDICATION OF
A POTENTIAL BIOMARKER SO IF YOU
WERE IN THE CLINIC AND YOU TOOK
A SKIN SAMPLE, WENT BACK AND
WERE ABLE TO SEQUENCE IT, ARE
THERE ANY PARTICULAR GENES THAT
WOULD TELL US OH, THIS PATIENT
ALSO HAS LYMPHOMA OR PEL OR MCD
OR KICS WE LOOK TO SEE WHETHER
THERE WAS ANYTHING SIGNIFICANT
AMONG THE CYTOKINES AND WE
DIDN'T SEE ANY GENES THAT WERE
SIGNIFICANTLY DIFFERENT BETWEEN
KS AND OTHER KEDS. WE DID
IDENTIFY ONE GENE THAT WAS
NOTABLE IN PROSTATE CANCER CELL
LINES THAT MAY BE HIGHER IN
THOSE WITH KS ALONE. THIS IS
ALSO NOTED IN THE LITERATURE TO
BE A TUMOR SUPPRESSOR GENE.
WHEN WE LOOK ACROSS SPECIFICALLY
THE GENE EXPRESSION PROFILES IN
THESE TUMORS, AGAIN, GI VERSUS
SKIN IN THE THREE PARTICIPANTS
WHO HAD BOTH, WE SEE
COMMONALITIES WITH THE LATENCY
PROGRAM ACROSS THESE TISSUES.
IRRESPECTIVE OF SITE AND
SIMILARLY THE GENE EXPRESSION
PROFILE OF VIRAL SIX IS SEEN IN
BOTH GI AND SKIN LESIONS SO THIS
WAS A LIMITED SAMPLE NUMBER. IT
WAS VERY EXCITING FOR OUR GROUP
BUT UNDERSTANDABLY WITH ALL THE
CAVEATS OF CAPTURING SAMPLES OF
THE TIME THAT PATIENTS PRESENT
WE THOUGHT, WELL, THE NEXT STEP
MAY BE TO LOOK AT ARCHIVAL
TISSUE SO THIS IS A PROJECT THAT
I AM VERY EXCITED ABOUT THAT HAS
BEEN BREWING AND ONGOING AND I
HAVE SOME PRELIMINARY RESULTS TO
SHARE. SO WE HAVE NOW -- I'VE
NOW BEEN LOOKING AT 43 PATIENTS
WITH SKIN KS THAT HAVE BEEN
SITTING IN THE LAB. AND WE HAVE
DONE NANO STRING BECAUSE IN OF
THESE PATIENTS, THERE'S LIMITED
INFORMATION THAT'S ACTUALLY IN
THE LITERATURE.
AND SO 53 OF THESE 43 PATIENTS,
53% OF THESE 43 PATIENTS HAVE KS
WITH OTHER KEDS. THEY HAVE LOW
HIV VIRAL LOADS AND VERY WELL
CONTROLLED HIV AND LOW CD4 COUNT
OF 175 CELLS PER MICROLITER SO
THE INITIAL CLUSTERING OF THESE
INITIAL HEAT MAPS OF THESE KS
TISSUES USING NANO STRING IS
ACTUALLY POINTING US TO SIMILAR
PATTERNS AS WHAT WE SEE WITH THE
BULK RNA SEQUENCING WITH
INCREASED LEVELS POTENTIALLY OF
SDC 1 AMONG THOSE WHO HAVE KS
ALONE. SO VALIDATING SOME OF
THE OBSERVATIONS THAT WE HAVE
SEEN IN OTHER EXPERIMENTS THAT
WE'VE DONE WITH KS IN THE CLINIC
AND THIS BECOMES VERY IMPORTANT.
THIS PARTICULAR PROJECT BECOMES
IMPORTANT AS WE'RE ABLE TO
ISOLATE THE EFFECTS OF CERTAIN
CLINICAL FACTORS PARTICULARLY
THE PRESENCE OF KEDS AND BECAUSE
THIS PLATFORM ALSO INCORPORATES
THE GENES CAN CORRELATE WHAT WE
SEE IN THE HOST AS COMPARED TO
EXPRESSION PROFILES OF KSHV
GENES AND THE EFFECT ON
LONGITUDINAL OUTCOMES. SO I
HAVE SHOWN YOU HERE THAT BOTH
SERUM, PBMCS AND TUMOR LESIONS
THEMSELVES ACTUALLY GIVE US
IMPORTANT INFORMATION THAT IS
THROUGHOUT THE THREAD SHOWING US
EVIDENCE OF INFLAMMATION BUT
THERE'S ALSO EVIDENCE OF A LOT
OF HETEROGENEITY AND THIS BRINGS
ME TO THE BIGGER POINT THAT THIS
IS A BIG CHALLENGE OF THE WORK
THAT I DO IS THAT THERE IS A LOT
OF HETEROGENEITY. AGAIN, ONE
VIRUS GIVES US NINE DIFFERENT
MANIFESTATIONS OF THIS DISEASE
AND A LOT OF THIS, A LOT OF THE
INFORMATION I PRESENTED SO FAR
HAS BEEN FROM OUR NATURAL
HISTORY STUDIES AT THE TIME OF
ACTIVE DISEASE. AND THE THING
ABOUT IT IS IT'S ALL GIVING US
INFORMATION, CYTOKINES AT THE
TIME OF DISEASE BUT NOT
NECESSARILY WHAT'S DRIVING THEM.
THE SITES THAT DRIVE SOME OF
THESE PROCESSES TO HAPPEN. AND
SO I WAS VERY LUCKY TO LEAD THIS
STUDY THAT ACTUALLY SEPARATES
PATIENT WHO IS HAVE KS AS
COMPARED TO CURRENT KEDS FROM
BASELINE ONWARDS IN THE STUDY OF
LIE POE SOME MALL. SO THIS
STUDY OF PO MA LID DO MID AND
LIPOSOMAL DOXORUBICIN ARE BOTH
LICENSED FOR USE IN KS.
AND THEY WERE COMBINED IN THIS
STUDY TO LOOK SPECIFICALLY ON
EFFECTS OF KS ALONE AS THOSE
COMPARED WITH OTHER KEDS SUCH AS
CASTLEMAN'S OR KICS. THIS
COMBINATION OF THERAPY WAS GIVEN
UNTIL THERE WAS A RESPONSE IN
KS.
UNTIL PROGRESSION OR UNTIL AS
THE PI, WE DETERMINE THAT THE
PATIENT COULD NO LONGER
PARTICIPATE. SO TO ILLUSTRATE
WHAT HAPPENS IN A CLINICAL TRIAL
WHAT WE DO, I WANTED TO TAKE YOU
THROUGH TO CASES, TWO CASES THAT
WERE PART OF THESE GROUPS SO
PATIENT NUMBER ONE AS WE'LL
REFER TO HIM WAS A -- IN GROUP
ONE WHO HAD KS ALONE WAS A
42-YEAR-OLD CAN IS SENDERED MAN
WORKING IN FASHION.
HE WAS DIAGNOSED WITH HIV IN
OCTOBER OF 2018 AND PROTECT --
PRESENTED IN KS ON HIS SKIN AND
LUNGS AND HAD OPPORTUNISTIC
INFECTIONS WHEN WE FIRST MET HIM
BUT HE HAD NO OTHER EVIDENCE OF
KICS OF MCD.
THIS IS HOW HIS KS LOOKED AT THE
TIME HE ENROLLED AND AS YOU CAN
SEE HERE ON THE CT SCAN EVIDENCE
OF INFILTRATES SHOWING HIS KS SO
IN TERMS OF OUR VENN DIAGRAM OF
COMBINATIONS HE SITS IN KS
ALONE. COMPARE THAT WITH
PARTICIPANT -- PATIENT TWO WHO
WAS IN GROUP TWO, WHO HAD KS
WITH KICS. HE WAS A 52-YEAR-OLD
CHRIS GENDERED MAN WHO WAS
STUDYING FOR A PH.D. MANY
MANAGEMENT.
HE WAS DIAGNOSED WITH HIV IN
2019 AND PROTECTS WITH SKIN KS,
KS IN HIS ORAL MUCOSA AND GI KS.
AGAIN, BOTH PATIENTS HAVE STAGE
ONE KS. AND HE HAS EVIDENCE OF
KICS. AND WE'LL TALK ABOUT THAT
IN THE NEXT SLIDE BUT THESE ARE
IMAGES OF PATIENTS WE ARE SEEING
IN THE CLINIC MOST OFTEN ON A
WEDNESDAY. SO YOU CAN SEE
EVIDENCE OF KS IN THIS GENTLEMAN
BOTH IN THE ORAL MEW KOE SASHGS
THE EYES AS WELL AS IN THE GI
TRACT. IN TERMS OF THE -- OF
WHERE THIS PARTICIPANT SITS IN
OUR VENN DIAGRAM HE SITS AS
SOMEONE WHO HAS KS AND KICS.
SO WE DID ADDITIONAL WORKUP IN
THIS PATIENT, AGAIN, TO MAKE
SURE THAT HE DID NOT HAVE
CASTLEMAN'S OR PEL AND WE SEE
THAT HE HAD AN ADDITIONAL BIOPSY
OF A LYMPH NODE THAT ALSO SHOWED
KS.
AND AS YOU CAN SEE ON THE SCREEN
HE DID HAVE ELEVATED KSHV VIRAL
LOAD OF OVER 4,000 COPIES IN HIS
CIRCULATION. CLEARLY WE
ESTABLISHED HIS DIAGNOSIS OF
KICS AND HE STARTS THE PROTOCOL
TO TREAT BOTH HIS KICS AND KS.
PARTICIPANT NUMBER ONE HAS -- AN
EXCELLENT PARTIAL RESPONSE IN
HIS KS HE RECEIVES EIGHT CYCLES
OF THERAPY PE HE GETS SOME DOSE
REDUCTION.
AND HAS THE CELLS TO LOW TO
SLIGHTLY ABOVE THAT. HIS
RESPONSE MIMICS WHAT WE SEE
AMONG A LOT OF THE PARTICIPANTS
WHERE WE SAW 79% RESPONSE RATE
WITH THE COMBINATION OF PA MA
LID DA MID. WHEREAS PARTICIPANT
TWO HAS A VERY DIFFERENT COURSE
IN GROUP TWO, ALTHOUGH HE HAS A
PARTIAL RESPONSE IN HIS KS AND
HIS KICS RESPONSE, HE CONTINUES
TO HAVE SYMPTOMS THAT WORSEN IN
JANUARY.
HE STOPS HIS THERAPY, AN
ADDITIONAL WORKUP IDENTIFIES
THAT HE HAS PRIMARY EFFUSION
LYMPHOMA. HE INITIATES
TREATMENT AT THE TIME BUT
UNFORTUNATELY BY MAY OF 2020 HE
DIES OF HIS LYMPHOMA. SO
CLEARLY WE HAVE A STUDY WHERE
TWO PATIENTS HAVE HIV AND KS AND
PRESENT VERY SIMILARLY. ONE
OBVIOUSLY WITH KICS AND THE
OTHER ONE DOESN'T. AND WHAT WE
SEE ON THIS GRAPH IS THAT THE
RESPONSE RATES ARE DIFFERENT IN
THIS STUDY BY THEIR DIAGNOSES.
SO THIS OFFERS US AN OPPORTUNITY
TO BETTER UNDERSTAND KEDS AS
THEY OCCUR IN KS IN THIS STUDY.
AND SO AS I APPROACH THIS, I
STARTED TO THINK, WELL, HOW CAN
WE USE THE CORRELATIVE SAMPLES
IN THE STUDY TO BETTER
UNDERSTAND AND DELINEATE THESE
DISEASES AS THEY OCCUR. I
IDENTIFIED A GROUP OF PATIENTS
BOTH IN GROUP ONE AND TWO. WHO
WERE ADJUSTED FOR THEIR BASELINE
CHARACTERISTICS SUCH AS AGE, CD4
T-CELLS, OBTAINED SERUM AT
BASELINE AND WE DID A THOROUGH
SYSTEMATIC APPROACH OF LOOKING
AT OMICS IN THESE PARTICIPANTS.
SO A SCAN WHICH IDENTIFIES 7,000
PROTEINS AS WELL AS BULK RNA
SEQUENCING IN THE CIRCULATION
AND FLOW CYTOMETRY. THUS, BEING
ABLE TO CATEGORIZE AT BASELINE
THESE TWO DISEASE PROCESSES IN
GROUP ONE VERSUS GROUP TWO. AND
FROM THE INITIAL FORAY INTO
THESE RESULTS WE IDENTIFY THAT
THOSE WHO WERE IN -- BETWEEN
GROUP ONE AND GROUP TWO, GROUP
ONE BEING THE GREEN AND GROUP
TWO BEING THE RED WE SEE SOME
SIGNIFICANT DIFFERENCES IN THE
IL-6 SIGNALLING. WE SEE THAT
THERE'S A SEPARATION AND THIS IS
PARTICULARLY IMPORTANT FOR TWO
REASONS, THE FIRST IS THAT THE
HIGHLIGHTED PROTEINS IL-6 AND
CSF 1 SUPPORT THE USE OF PROCRIT
ANYBODY WHICH IS A STUDY THAT
WE'RE LAUNCHING THAT HAS
PATIENTS WHO HAVE KICS WITH KS
OR CASTLEMAN'S WITH KS JOINING
IN THIS TRIAL AND THIS IS A CSF
R1 INHIBITOR THAT IS LICENSED
FOR FIBROSIS AND THIS MAY BYPASS
SOME OF THE ISSUES WE SAW WITH
IL-6 JUST IL-6 INHIBITION ITSELF
BY SPECIFICALLY ADDRESSING MOST
OF THE DOWNSTREAM EFFECTS OF --
UPSTREAM EFFECTS OF IL-6 AND THE
SECOND REASON WHY THIS PROTEOMIC
ANALYSIS IS IMPORTANT IS IT
HELPS US GET A SET OF DATA AND
PROTEINS THAT MAY BE USED FOR
DIAGNOSIS OF PATIENTS BETWEEN KS
AND KS CAN OTHER KEDS THAT WE
PLAN TO VALIDATE IN LARGER
POPULATIONS.
AND WITH THIS IN MIND, WE'RE
ALSO EXCITED TO SEE THAT
COMPARING GROUP ONE VERSUS TWO,
WE'VE STARTED TO SEE THAT THE
BULK RNA SEQUENCING AND
PROTEOMIC PATHWAYS ARE CLEARLY
HIGHER IN GROUP TWO, AGAIN,
SUPPORTING OUR UNDERSTANDING
THAT THIS IS A PROINFLAMMATORY
CONDITION. FINALLY, THINKING
ABOUT THE FLOW CYTOMETRY RESULTS
FROM THESE ANALYSES OF PATIENTS
ON THE STUDY, WE SEE THAT AS WE
EXPECTED FROM OUR INFLAMMASOME
WORK, ELEVATED INTERMEDIATE
MONOCYTES IN THOSE WITH MCD,
KICS, AND KS COMPARED TO KS
ALONE. WE ALSO SEE ACTIVATED
T-CELL PROFILES IN THOSE WITH KS
AND OTHER KEDS. AND THIS IS
INTERESTING BECAUSE WE'VE SEEN
SOME OF THESE ACTIVATED T-CELLS
ARE ALSO INCREASED IN PATIENTS
WITH COVID AND ARE OFTEN
ASSOCIATED WITH SEVERITY OF
COVID. AND THAT TAKES US TO THE
NEXT STEP WHICH IS REALLY
DELVING INTO THE EFFECTS OF THE
VIRUS ITSELF, KSHV AND HOW THIS
INFLUENCES SOME OF THE THINGS
WE'RE SEEING BOTH IN THE
PROTEIN, THE RNA SEQUENCING AS
WELL AS THE FLOW CYTOMETRY
RESULTS AND SO TOGETHER WE'RE
ABLE TO BUILD A COMPREHENSIVE
PROFILE THAT HELPS DELINEATE
PATIENTS WHO HAVE KS ALONE
VERSUS THOSE WHO HAVE KS WITH
OTHER KEDS, THUS SUPPORTING THE
PLAN TO DEVELOP NEW DIAGNOSTICS
FOR THESE DISEASES. SO LOOKING
TO THE FUTURE, I HAVE LEARNED A
LOT IN MY JOURNEY SO FAR TO TRY
TO DELINEATE THESE DISORDERS AND
WITH THE PLAN I HAVE FOR ONGOING
CLINICAL TRIALS I AIM TO
INCORPORATE WHAT I LEARNED BY
COLLECTING SYSTEMICALLY BLOOD
AND TISSUE OVER TIME POINTS FOR
THE STUDIES THAT I'M RUNNING: I
HAVE LISTED THEM ON THE SCREEN
HERE BUT THEY INCLUDE STUDIES OF
A CDK 46 INHIBITOR AND KS. A
CYTOKINES INCLUDING IL-12 AND 7
IN KS AS WELL AS THE STUDY I
MENTIONED. AND IN DOING SO I
HOPE TO CREATE A BETTER
UNDERSTANDING OF THE VIRUS, THE
INTERACTION, THE IMMUNE SYSTEM,
AND THE EFFECTS OF THE TREATMENT
OF THESE DISORDERS. AND SO,
WITH THAT, I THANK YOU, AGAIN,
FOR THE OPPORTUNITY TO CHAT WITH
YOU TODAY AND IT'S IMPORTANT
THAT I THANK MY WONDERFUL BRANCH
WHO ARE HERE. DR. LORRAINE,
FUTURE DOCTOR. THE CREW LAB.
OUR MANY, MANY RESEARCHERS AND
MANY OF WHOM ARE LISTENING, MY
MENTORSHIP COMMITTEE. OUR
COLLABORATORS AND OUR PATIENTS
WHO ARE THE MOST IMPORTANT THING
AND THE REASON MANY OF US GET UP
IN THE MORNING SO THANK YOU VERY
MUCH FOR YOUR TIME.
>> AUDIENCE: (APPLAUSE).
>> ANY QUESTIONS.
>> AUDIENCE: GREAT TO SEE YOU.
FANTASTIC TALK AS ALWAYS. I'VE
PROBABLY ASKED THIS QUESTION IN
DIFFERENT WAYS BEFORE. THE
PATIENT, THE LAST PATIENT YOU
PRESENTED WHO, YOU KNOW, COMES
IN WITH KS AND KICS AND HAS
UNCONTROLLED INFLAMMATION AND
THEN HAS PEL. AT WHAT STAGE DO
YOU THINK HE HAS P EL. I KNOW
IT'S IMPOSSIBLE TO SAY. DO YOU
THINK IT'S A GENE THAT SETS THIS
OFF OR IS IT THE UNCONTROLLED
INFLAMMATORY RESPONSE WITH THIS
REPLICATION OF INFLAMMATORY
STIMULI CAUSED THIS TO EVOLVE.
DO WE HAVE HYPOTHESES ON THAT?
>> THANK YOU, JOE, GOOD TO SEE
YOU TOO. SO THERE'S A COHORT OF
OUR PATIENTS WHO HAVE
CASTLEMAN'S WHO THEN GO TO
HAVING PEL AND I THINK THAT
GROUP OF PATIENTS ARE PROBABLY
THE BEST GROUP TO ANSWER YOUR
QUESTION. PARTICULARLY TO
UNDERSTAND WHY THESE CELLS THAT
ARE POLYCLONAL THEN GO INTO A
MONOCLONAL B-CELL PROCESS. I
GET THE -- IT'S PROBABLY
COMBINATION OF THINGS AND THAT
THERE IS SOME SORT OF VIRAL
COMPONENT THAT DRIVE THOSE
B-CELLS TO GO FROM A POLYCLONAL
PROCESS TO A MONOCLONAL PROCESS.
THAT BEING SAID, WE -- WE ARE
UNDERSTANDING KICS AS AN ENTITY
MORE AND MORE OVER TIME. THE
INITIAL REPORTS OF KICS INCLUDED
PATIENTS WITH PEL AND WE'RE
SEEING MORE AND MORE THAT PEL IS
A DISTINCT ENTITY AND AS YOU
STUDY HLH AS WELL THESE ARE
PATIENTS WITH MORE OF THE HLH
PHENOTYPE AS COMPARED TO THOSE
WITH KICS. SO TO YOUR QUESTION
I THINK THAT A LOT OF THESE
PATIENTS HAVE PEL SITTING AROUND
BUT THE DIAGNOSTIC POSSROCESSESE
SO CHALLENGING IN THESE PATIENTS
AND THERE ARE SO FEW CELLS THAT
THAT ITSELF PRESENTS THE
ADDITIONAL ROADBLOCK.
>> AUDIENCE: ONE FOLLOW UP
QUESTION IF I COULD ASK IT. SO
WITH THE PA CAT ANYBODY WHICH I
THINK IS FANTASTIC AND REALLY
LOOKING FORWARD TO SEEING WHAT
YOU FIND ARE THERE ANY CONCERNS,
I LOVE GIVING IMMUNOSUPPRESSION
WITH PEOPLE WITH INFECTIONS BUT
ANY CONCERNS WITH THE INHIBITOR
SPECIFICALLY AND VIRUSES BECOME
A PROBLEM WITH KSHV BECOMING A
BIT MORE UNCONTROLLED WITH THAT?
>> THIS IS A VERY SPECIFICALLY
TARGETED INHIBITOR AS COMPARED
TO OTHERS ON THE MARKET. SO WE
WILL BE KEEPING A VERY CLOSE
MONITORING ON OPPORTUNISTIC
INFECTIONS. THANKS WITH THE
HELP OF OUR NYAD COLLEAGUES AS
WELL.
>> AUDIENCE: FANTASTIC.
>> THANK YOU. OKAY. I THINK
WE'RE GOOD. ALL RIGHT, THANK
YOU SO MUCH. OH -- WAS THERE A
QUESTI
QUESTION?
>> AUDIENCE: GREAT TALK. IS THE
INCIDENCE OF KICS OR KS
DEPENDENT ON THE PARTICULAR
SUBTYPE OF HIV INFECTION IN IS
THERE ANY RELATIONSHIP TO THE
(SPEAKER FAR FROM MIC).
>> I DON'T THINK IT IS. I DON'T
THINK WE SEE THAT AS MUCH BUT
THAT'S A GOOD THOUGHT. WE -- I
DON'T THINK WE'VE LOOKED IN
DETAIL BUT IT IS A GOOD THOUGHT
AND I DON'T THINK IT IS BUT WE
SHOULD LOOK. THANK YOU. ALL
RIGHT. OKAY, I THINK WE'RE NOW
DONE. THANK YOU.
>> AUDIENCE: (APPLAUSE).