CME - CP 2023
CONTINUING MEDICAL
EDUCATION CLINICAL
PATHOLOGY 2023
6 - 7 October 2024, Hotel Santika Gubeng, Surabaya
Microenvironment of tumor
Hartono Kahar
CME-CP 2023
The critical role of laboratory medicine in the global
response from initial diagnosis of patient monitoring and
treatment.
CME - CP 2023
CONTINUING MEDICAL
EDUCATION CLINICAL
PATHOLOGY 2023
6 - 7 October 2024, Hotel Santika Gubeng, Surabaya
Incidences of Cancer (Both sexes)
Incidence Male: Prostate, Lung, colorectal
Incidence Female: Breast cancer, cervix, liver
New cases: 19.3 million
Deaths 9.9 million
Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.
doi: 10.3322/caac.21660. VOLUME 71 | NUMBER 3 | MAY/JUNE 2021 Available online at cacancerjournal.com.
CME - CP 2023
Development of metastatic cancer CONTINUING MEDICAL
EDUCATION CLINICAL
PATHOLOGY 2023
6 - 7 October 2024, Hotel Santika Gubeng, Surabaya
Development of metastatic cancer
- Cancer cells: disease are
concisting of transformed
cells with cell autonomous
hyperproliferative, invasisive,
limitless survival capacities.
- Tumor micro environment
(TME) as new integrated
and part of cancer tissue
- TME contribution to tumor
evolution and metastasis.
Galon and Bruni, 2022.Tumor Immunology and Tumor Evolution: Intertwined Histories. Immunity 52, January 14, 2020
Lorusso and Ruegg, 2008. The tumor microenvironment and its contribution to tumor evolution to wrad metastasis. Histochem cell biol.
CME - CP 2023
CONTINUING MEDICAL
EDUCATION CLINICAL
PATHOLOGY 2023
6 - 7 October 2024, Hotel Santika Gubeng, Surabaya
Tumor Microenvironment/ TME composition
Celluler:
a. innate immune cells:
macrophage,
neutrophils,Dendrite cellc/DCs,
innate lymphocyte, myeloid
inhibitor cells, nK cells.
b. B. Adaptive immune cells: T cells,
bcells. CD8+ tcells /CTLs.
Non-Celluler:
endothelial cells, fibroblast,
tissue specific cells.
Wang et al, 2020. Role of tumor microenvironment in cancer progression and therapeutic strategy. Cancer Medicine. 2023;12:11149–
11165. wileyonlinelibrary
CME - CP 2023
CONTINUING MEDICAL
EDUCATION CLINICAL
PATHOLOGY 2023
6 - 7 October 2024, Hotel Santika Gubeng, Surabaya
Roles of TME in cancer cells: Anti-tumor immune
microenvironment
• CTLs (CD8+) detect abnormal Ag ca
cells will destruction cacer cells juga
sekresi (IFN-gamma)
• TH1 → pro inflamasi
• CD4+ support CD8+→ secret IL2 and
IFN-gama
• T regulatory → suppress inflamantory
responses and control autoimmune.
Wang et al, 2020. Role of tumor microenvironment in cancer progression and therapeutic strategy. Cancer Medicine. 2023;12:11149–
11165. wileyonlinelibrary
CME - CP 2023
CONTINUING MEDICAL
EDUCATION CLINICAL
PATHOLOGY 2023
6 - 7 October 2024, Hotel Santika Gubeng, Surabaya
Roles of TME in cancer cells: Immune suppressive
microenvironment
• Treg→ secrete IL-2→ modulasi
homeostasis and function NK
• Treg→ growth factors
• B cells: IL-10, TGF-beta→ promote
immune suppressive→ macrophage,
neutrophil, Cytotoxic T cells.
Wang et al, 2020. Role of tumor microenvironment in cancer progression and therapeutic strategy. Cancer Medicine. 2023;12:11149–
11165. wileyonlinelibrary
CME - CP 2023
CONTINUING MEDICAL
EDUCATION CLINICAL
PATHOLOGY 2023
6 - 7 October 2024, Hotel Santika Gubeng, Surabaya
Roles of TME in cancer cells: cross-talk signal mechanism
in immune cells.
• Inflamantory cytokine (IFNs): CD8+
T lymphocyte (CTLs) and Natural
killer (NK)→regulate various
biological activities: immune
respone, cell proliferation, viral
infection→cell proliferation,
metastasis, therapy resistance
• IFN-ᵧ regulasi CML stem cells to
induces proliferation and
differentiation.
• IL-6:macrophage, T cells,
fibroblast→ maintain pro
TME→tumor evasion and
angiogenesis.
Nallasamy et al. 2022. Tumor microenvironment enriches the stemness features: the architectural event of therapy resistance and metastasis.
Molecular Cancer (2022) 21:225 https://doi.org/10.1186/s12943-022-01682-x
CME - CP 2023
CONTINUING MEDICAL
EDUCATION CLINICAL
PATHOLOGY 2023
6 - 7 October 2024, Hotel Santika Gubeng, Surabaya
Roles of TME in cancer cells: cross-talk signal mechanism
in immune cells.
• IL-6:
• stemness enrichment of cancer cells, self-renewal properties
of CD133 lung cancer, DNA repair.
• IL-6 regulate JAK2/STAT axis up-regulate DN-
methyltransferase 1 (DNMT1)
• Myeloid derived suppressor cells (MDCs): vital component TME→
as major immune resoponse regulator and key key target for
cancer treatment.
• Tumor-associated macrophage (TAM):
• M1-Macrophage→ initiate immune response
• M2-Macrophage: activated by IL-4, IL-10, IL-13→polyamine,
proline→ proliferation and collagen production→ as tumor
infiltrating cells (solid malignancy)→proliferation, invasion,
migration, metastasis.
Nallasamy et al. 2022. Tumor microenvironment enriches the stemness features: the architectural event of therapy resistance and metastasis.
Molecular Cancer (2022) 21:225 https://doi.org/10.1186/s12943-022-01682-x
CME - CP 2023
CONTINUING MEDICAL
EDUCATION CLINICAL
PATHOLOGY 2023
6 - 7 October 2024, Hotel Santika Gubeng, Surabaya
Roles of TME in cancer cells: cross-talk signal mechanism
in immune cells.
• Endothelial cells mediated stemness maintenance:
• supporting system→ blood vessel, remodel and extend blood
vessels network and tissue growth.
• Secrete endocrine factors→ tumor development. Tumor
endothelium as potential target therapy.
• Adipocytes-mediated stemness maintenance:
• Energy-storing fat cells
• Cancer-associated supporting adipocytes secreted adipokines,
cytokines, growth factors→inhibited signaling to tumor and
induced steamness enrichment.
Nallasamy et al. 2022. Tumor microenvironment enriches the stemness features: the architectural event of therapy resistance and metastasis.
Molecular Cancer (2022) 21:225 https://doi.org/10.1186/s12943-022-01682-x
CME - CP 2023
CONTINUING MEDICAL
EDUCATION CLINICAL
PATHOLOGY 2023
6 - 7 October 2024, Hotel Santika Gubeng, Surabaya
Key TME component , stemness factors and their
function in cancer stem cells (CSCs)
Nallasamy et al. 2022. Tumor microenvironment enriches the stemness features: the architectural event of therapy resistance and metastasis.
Molecular Cancer (2022) 21:225 https://doi.org/10.1186/s12943-022-01682-x
CME - CP 2023
CONTINUING MEDICAL
EDUCATION CLINICAL
PATHOLOGY 2023
6 - 7 October 2024, Hotel Santika Gubeng, Surabaya
Key TME component , stemness factors and their
function in cancer stem cells (CSCs)
Nallasamy et al. 2022. Tumor microenvironment enriches the stemness features: the architectural event of therapy resistance and metastasis.
Molecular Cancer (2022) 21:225 https://doi.org/10.1186/s12943-022-01682-x
CME - CP 2023
CONTINUING MEDICAL
EDUCATION CLINICAL
PATHOLOGY 2023
6 - 7 October 2024, Hotel Santika Gubeng, Surabaya
Laboratory examination of TME
Karakteristik metode pemeriksaan laboratorium TEM: immunositochemistry, imaging mass cytometri, flow
cytometri, RNA seq dan Spatial transcriptomic
Simonaggio ET AL. 2021. Tumor Microenvironment Features as Predictive Biomarkers of Response to Immune Checkpoint Inhibitors (ICI) in
Metastatic Clear Cell Renal Cell Carcinoma (mccRCC). Cancers 2021, 13, 231
CME - CP 2023
CONTINUING MEDICAL
EDUCATION CLINICAL
PATHOLOGY 2023
6 - 7 October 2024, Hotel Santika Gubeng, Surabaya
Cytometric bead array (CBA)
• Flow cytometric bead-based technology: simultaneously multiple analytes in biological samples.
• CBA systems enable this multiple detection in sample volumes too small for traditional immunoassays
• CBA also allows for the design and creation of assays to measure a variety of analytes including
inflammatory mediators, chemokines, immuno-globulin isotypes, intracellular signaling molecules,
apoptotic mediators, adhesion molecules, and antibodies
Karina Andrea Go´ mez and Carlos Andre´ s Buscaglia (eds.), T. cruzi Infection: Methods and Protocols, Methods in Molecular Biology,
vol. 1955, https://doi.org/10.1007/978-1-4939-9148-8_23, © Springer Science+Business Media, LLC, part of Springer Nature 2019
CME - CP 2023
CONTINUING MEDICAL
EDUCATION CLINICAL
PATHOLOGY 2023
6 - 7 October 2024, Hotel Santika Gubeng, Surabaya
Advantage and limitation some immunoassay methods
TERIMA KASIH ATAS
PERHATIANNYA
