Investigation of sex-biased differences in anti-cancer immune responses
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| Sprache: | English |
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2022
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| 100 | 1 | |a Vargas-Delgado, María-Elena |e Verfasser |4 aut | |
| 245 | 1 | 0 | |a Investigation of sex-biased differences in anti-cancer immune responses |c by María-Elena Vargas-Delgado, M. Sc. |
| 264 | 1 | |a Hamburg |c 2022 | |
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| 502 | |b Dissertation |c Universität Hamburg |d 2022 | ||
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Datensatz im Suchindex
| _version_ | 1819746905551273984 |
|---|---|
| adam_text | TABLE
OF
CONTENTS
SUMMARY
............................................................................................................
6
ZUSAMMENFASSUNG
.................................................................................................................................
7
LIST
OF
ABBREVIATIONS
.............................................................................................................................
8
1.
INTRODUCTION
.....................................................
11
1.1.
SEX
DIFFERENCES
IN
IMMUNITY
...........................................................................................................
11
1.1.1.
FACTORS
DRIVING
SEX
DIFFERENCES
IN
IMMUNITY
................................................................................
12
L.L.L.L.
SEX
CHROMOSOMES
IN
IMMUNITY
...............................................................................................
12
I.I.I.2.
SEX
HORMONES
IN
IMMUNITY
......................................................................................................
13
LL.1.2.1.
ESTROGEN/ER
SIGNALING
IN
IMMUNITY
...................................................................................
15
I.I.I.2.2.
ANDROGEN/AR
SIGNALING
IN
IMMUNITY
.................................................................................
15
1.1.13.
OTHER
FACTORS
INFLUENCING
SEX
DIFFERENCES
IN
IMMUNITY
...........................................................
18
1.2.
SEX
DIFFERENCES
IN
CANCER
.................................................................................................................19
1.2.1.
MECHANISMS
OF
SEX
DIFFERENCES
IN
CANCER
....................................................................................
21
1.2.1.1.
SEX
CHROMOSOMES
IN
CANCER
....................................................................................................
22
1.2.1.2.
SEX
HORMONES
IN
CANCER
..........................................................................................................
22
1.2.2.
SEX
DIFFERENCES
IN
CANCER
THERAPY
................................................................................................
24
I.2.2.I.
THERAPEUTIC
APPROACHES
FOR
CANCER
TREATMENT
.......................................................................
24
I.2.2.2.
SEX-BIASED
OUTCOMES
IN
CANCER
THERAPIES
...............................................................................
25
I.2.2.2.I.
SEX
DIFFERENCES
AND
CANCER
IMMUNE
THERAPIES
.................................................................
26
1.3.
AIMS
....................................................................................................................................................
29
2.
MATERIALS
AND
METHODS
...........................................................................................................
30
2.1.
MATERIALS
............................................................................................................................................
30
2.1.1.
CHEMICALS
AND
REAGENTS
................................................................................................................
30
2.1.2.
BUFFERS
AND
SOLUTIONS
....................................................................................................................
31
2.1.3.
KITS,
PLASMIDS
AND
PREMADE
REAGENTS
...........................................................................................
32
2.1.4.
PRIMERS
..........................................................................................................................................
32
2.1.5.
ANTIBODIES
AND
STAINING
REAGENTS
.................................................................................................
33
2.1.6.
ENZYMES........................................................................................................................................
34
2.1.7.
CELL
LINES
AND
PRIMARY
CELLS
...........................................................................................................
34
2.1.8.
UTILITIES
..........................................................................................................................................
35
2.1.9.
MACHINES
.......................................................................................................................................
35
2.1.10.
SOFTWARE
........................................................................................................................................
36
2.1.11.
STATISTICS
.......................................................................................................................................
36
2.2.
METHODS
..............................................................................................................................................
37
2.2.1.
IN
VITRO
..........................................................................................................................................
37
2.2.1.1.
CELL
CULTURE
..............................................................................................................................
37
2.2.1.2.
CULTURE
CONDITIONS
OF
ADHERENT
CELLS
.......................................................................................
37
2.2.1.3.
CULTURE
CONDITIONS
OF
SUSPENSION
CELLS
....................................................................................
38
2.2.1.4.
CHARCOAL
STRIPPING
OF
FBS
FOR
SEX
HORMONE
VIABILITY
ASSAY
......................................................
38
2.2.1.5.
CLONING
OF
A
TDTOMATO
AND
OVALBUMIN
PLASMID
.......................................................................
38
2.2.1.6.
GENERATION
OF
STABLE
TRANSDUCTIONS
BY
LENTIVIRAL
TRANSFECTION
.................................................
40
2.2.1.7.
ISOLATION
OF
RNA
........................................................................................................................
41
2.2.1.8.
CDNA
SYNTHESIS.........................................................................................................................
42
2.2.1.9.
QUANTITATIVE
REAL-TIME
PCR
.......................................................................................................
42
2.2.1.10.
CELL
VIABILITY
ASSAY
WITH
SEX
HORMONE
TREATMENT
................................................................
43
2.2.1.11.
ENZYME
LINKED
IMMUNOSORBENT
ASSAY
(ELISA)
TESTOSTERONE
MOUSE
..................................
43
2.2.1.12.
FLOW
CYTOMETRY
ANALYSES
.....................................................................................................
44
2.2.1.12.1.
CELL
STAINING
FOR
INTRACELLULAR
TRANSCRIPTION
FACTORS
........................................................
45
2.2.1.13.
CO-CULTURE
EXPERIMENTS
......................................................................................................
46
2.2.1.13.1.
CO-CULTURE
OF
OT-1
SPLENOCYTES
WITH
TUMOR
CELL
LINES
.....................................................
46
2.2.1.13.2.
SEX
HORMONE
TREATMENTS
ON
CO-CULTURES
OF
MURINE
CD8
+
T
OT-1
SPLENOCYTES
AND
MURINE
TUMOR
CELL
LINES
.....................................................................................................................................
47
2.2.2.
IN
VIVO
...........................................................................................................................................
48
2.2.2.1.
ANIMALS
AND
ETHICAL
REGULATIONS
..............................................................................................
48
2.2.2.2.
EXPERIMENTAL
TUMOR
MODELS
.....................................................................................................
48
2.2.2.3.
LOCAL
TUMOR
INDUCTION
..............................................................................................................
48
2.2.2.4.
LEUKEMIA
INDUCTION
..................................................................................................................
49
2.2.2.5.
TREATMENTS
..............................................................................................................................
49
2.2.2.6.
SURGICAL
PROCEDURES
.................................................................................................................
49
2.2.2.6.1.
ORCHIECTOMY
.....................................................................................................................
50
2.2.2.6.2.
OSMOTIC
PUMP
IMPLANTATION
.............................................................................................
50
2.2.2.7.
ORGAN
HARVEST
&
GENERATION
OF
SINGLE
CELL
SUSPENSIONS
IN
THE
MOUSE
.....................................
50
2.2.2.7.1.
SINGLE-CELL
SUSPENSION
FROM
MURINE
BLOOD
........................................................................
50
2.2.2.7.2.
SINGLE-CELL
SUSPENSION
FROM
MURINE
TUMOR
.......................................................................
51
2.2.2.7.3.
SINGLE-CELL
SUSPENSION
FROM
MURINE
SPLEEN
......................................................................
51
2.2.2.7.4.
SINGLE-CELL
SUSPENSION
FROM
MURINE
BONE
MARROW
...........................................................
52
3.
RESULTS...............................................................................................................................................
53
3.1.
PROGRESSION
AND
SURVIVAL
ARE
SEX-BIASED
IN
MURINE
AML
............................................................
53
3.2.
SEX
HORMONE
TREATMENT
DOES
NOT
HAVE
A
DIRECT
INFLUENCE
ON
AML
CELL
PROLIFERATION
........
54
4
3.3.
GENETICALLY-ENGINEERED
OVA-EXPRESSING
TUMOR
CELLS
ARE
ABLE
TO
INDUCE
CD8
T
CELL
SPECIFIC
IMMUNE
RESPONSES
........................................................................................................................................
55
3.4.
TESTOSTERONE
TREATMENT
OF
CANCER-SPECIFIC
CD8+
T
CELLS
INDUCES
IMMUNOSUPPRESSION
........
56
3.5.
MALES
RESPOND
MORE
EFFECTIVELY
TO
PDI
BLOCKADE
IN
CRC
MODEL
.............................................
57
3.6.
CASTRATED
MALES
PHENOCOPY
THE
RESPONSE
RATE
OF
FEMALE
MICE
TO
PDI
BLOCKADE
................
60
3.7.
FEMALES
WITH
TESTOSTERONE
RESPONDED
BETTER
TO
ANTI-PDL
COMPARED
TO
FEMALES,
MIMICKING
MALE
RESPONSE
............................................................................................................................
64
3.8.
TESTOSTERONE
SUPPLEMENTATION
LEADS
TO
INCREASED
MEMORY-LIKE
SELF-RENEWAL
PRECURSOR
CELLS
UPON
PDI
BLOCKADE
..............................................................................................................................
66
3.9.
TESTOSTERONE
SUPPLEMENTATION
TRIGGERS
AND
HELPS
MAINTAIN
POOL
OF
MEMORY-LIKE
SELF
RENEWAL
PRECURSOR
CELLS
UPON
PDI
BLOCKADE
............................................................................................
68
3.10.
TUMOR
GROWTH
RATE
SHOWS
A
MALE
DISADVANTAGE
AND
MORE
EFFECTIVE
TO
PDI
BLOCKADE
IN
LUNG
CANCER
MODEL
.........................................................................................................................................
71
3.11.
MALE
SEX
LEADS
TO
INCREASED
CD8
TCF1*PD1*
T
CELLS
UPON
ANTI-PDL
BLOCKADE
IN
LUNG
CANCER
MODEL
72
4.
DISCUSSION
........................................................................................................................................
76
4.1.
ARE
SEX
DIFFERENCES
IN
HEMATOLOGICAL
MALIGNANCIES
AND
SOLID
CANCERS
DRIVEN
BY
SEX
DIMORPHIC
IMMUNE
RESPONSES?
...................................................................................................................
77
4.2.
CAN
ANDROGENS
INFLUENCE
ICB
RESPONSE
REGARDLESS
OF
THE
BIOLOGICAL
SEX?
............................
79
4.3.
ARE
ANDROGENS
ABLE
TO
INFLUENCE
ICB
RESPONSE
BY
MODULATING
CD8
+
T
CELL
SUBSETS?
..........
81
4.4.
ANDROGENS
AND
TCF1
IN
CANCER
:
DETRIMENTAL
OR
BENEFICIAL?
....................................................
83
4.5.
THERAPEUTIC
IMPLICATIONS
................................................................................................................
85
4.6.
MODELING
THE
AR/TCF1
SIGNALING
MODE
OF
ENHANCING
ANTI-PDL
THERAPY
...............................
86
5.
CONCLUSION
AND
FINAL
REMARKS
.............................................................................................
88
REFERENCES
................................................................................................................................................
89
PUBLICATIONS
...........................................................................................................................................
98
ACKNOWLEDGEMENTS
...........................................................................................................................
99
DECLARATION
OF
OATH
........................................................................................................................
100
5
|
| any_adam_object | 1 |
| author | Vargas-Delgado, María-Elena |
| author_facet | Vargas-Delgado, María-Elena |
| author_role | aut |
| author_sort | Vargas-Delgado, María-Elena |
| author_variant | m e v d mevd |
| building | Verbundindex |
| bvnumber | BV048929795 |
| ctrlnum | (OCoLC)1348394431 (DE-599)DNB1273397533 |
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| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
| genre_facet | Hochschulschrift |
| id | DE-604.BV048929795 |
| illustrated | Illustrated |
| indexdate | 2024-12-24T09:44:51Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-034193763 |
| oclc_num | 1348394431 |
| open_access_boolean | |
| owner | DE-355 DE-BY-UBR |
| owner_facet | DE-355 DE-BY-UBR |
| physical | 101 Blätter Illustrationen 30 cm |
| publishDate | 2022 |
| publishDateSearch | 2022 |
| publishDateSort | 2022 |
| record_format | marc |
| spellingShingle | Vargas-Delgado, María-Elena Investigation of sex-biased differences in anti-cancer immune responses |
| subject_GND | (DE-588)4113937-9 |
| title | Investigation of sex-biased differences in anti-cancer immune responses |
| title_auth | Investigation of sex-biased differences in anti-cancer immune responses |
| title_exact_search | Investigation of sex-biased differences in anti-cancer immune responses |
| title_full | Investigation of sex-biased differences in anti-cancer immune responses by María-Elena Vargas-Delgado, M. Sc. |
| title_fullStr | Investigation of sex-biased differences in anti-cancer immune responses by María-Elena Vargas-Delgado, M. Sc. |
| title_full_unstemmed | Investigation of sex-biased differences in anti-cancer immune responses by María-Elena Vargas-Delgado, M. Sc. |
| title_short | Investigation of sex-biased differences in anti-cancer immune responses |
| title_sort | investigation of sex biased differences in anti cancer immune responses |
| topic_facet | Hochschulschrift |
| url | https://d-nb.info/1273397533/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034193763&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT vargasdelgadomariaelena investigationofsexbiaseddifferencesinanticancerimmuneresponses |