PMID- 36276271
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221025
IS  - 1687-8450 (Print)
IS  - 1687-8469 (Electronic)
IS  - 1687-8450 (Linking)
VI  - 2022
DP  - 2022
TI  - A Machine Learning Workflow of Multiplexed Immunofluorescence Images to 
      Interrogate Activator and Tolerogenic Profiles of Conventional Type 1 Dendritic 
      Cells Infiltrating Melanomas of Disease-Free and Metastatic Patients.
PG  - 9775736
LID - 10.1155/2022/9775736 [doi]
LID - 9775736
AB  - Melanoma is the deadliest form of skin cancer. Due to its high mutation rates, 
      melanoma is a convenient model to study antitumor immune responses. Dendritic 
      cells (DCs) play a key role in activating cytotoxic CD8(+) T lymphocytes and 
      directing them to kill tumor cells. Although there is evidence that DCs 
      infiltrate melanomas, information about the profile of these cells, their 
      activity states, and potential antitumor function remains unclear, particularly 
      for conventional DCs type 1 (cDC1). Approaches to profiling tumor-infiltrating 
      DCs are hindered by their diversity and the high number of signals that can 
      affect their state of activation. Multiplexed immunofluorescence (mIF) allows the 
      simultaneous analysis of multiple markers, but image-based analysis is 
      time-consuming and often inconsistent among analysts. In this work, we evaluated 
      several machine learning (ML) algorithms and established a workflow of 
      nine-parameter image analysis that allowed us to study cDC1s in a reproducible 
      and accessible manner. Using this workflow, we compared melanoma samples between 
      disease-free and metastatic patients at diagnosis. We observed that cDC1s are 
      more abundant in the tumor infiltrate of the former. Furthermore, cDC1s in 
      disease-free patients exhibit an expression profile more congruent with an 
      activator function: CD40(high)PD-L1(low) CD86(+)IL-12(+). Although disease-free 
      patients were also enriched with CD40(-)PD-L1(+) cDC1s, these cells were also 
      more compatible with an activator phenotype. The opposite was true for metastatic 
      patients at diagnosis who were enriched for cDC1s with a more tolerogenic 
      phenotype (CD40(low)PD-L1(high)CD86(-)IL-12(-)IDO(+)). ML-based workflows like 
      the one developed here can be used to analyze complex phenotypes of other immune 
      cells and can be brought to laboratories with standard expertise and computer 
      capacity.
CI  - Copyright (c) 2022 Sarai G. De Leon Rodriguez et al.
FAU - De Leon Rodriguez, Sarai G
AU  - De Leon Rodriguez SG
AUID- ORCID: 0000-0002-2451-0123
AD  - UMAE Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto 
      Mexicano del Seguro Social, Unidad de Investigacion Medica en Inmunoquimica, 
      Mexico City, Mexico.
AD  - Posgrado en Ciencias Biologicas, Universidad Nacional Autonoma de Mexico, Mexico 
      City, Mexico.
FAU - Hernandez Herrera, Paul
AU  - Hernandez Herrera P
AUID- ORCID: 0000-0002-2206-3489
AD  - Laboratorio Nacional de Microscopia Avanzada, Universidad Nacional Autonoma de 
      Mexico, Cuernavaca, Morelos, Mexico.
FAU - Aguilar Flores, Cristina
AU  - Aguilar Flores C
AUID- ORCID: 0000-0001-5317-4731
AD  - UMAE Hospital de Pediatria, Centro Medico Nacional Siglo XXI, Instituto Mexicano 
      del Seguro Social, Unidad de Investigacion Medica en Inmunologia, Mexico City, 
      Mexico.
FAU - Perez Koldenkova, Vadim
AU  - Perez Koldenkova V
AUID- ORCID: 0000-0001-9118-8800
AD  - Laboratorio Nacional de Microscopia Avanzada-IMSS, Division de Desarrollo de La 
      Investigacion, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro 
      Social, Mexico City, Mexico.
FAU - Guerrero, Adan
AU  - Guerrero A
AUID- ORCID: 0000-0002-4389-5516
AD  - Laboratorio Nacional de Microscopia Avanzada, Universidad Nacional Autonoma de 
      Mexico, Cuernavaca, Morelos, Mexico.
FAU - Mantilla, Alejandra
AU  - Mantilla A
AUID- ORCID: 0000-0002-5085-6216
AD  - Servicio de Patologia, Hospital de Oncologia Centro Medico Nacional Siglo XXI, 
      Instituto Mexicano del Seguro Social, Mexico City, Mexico.
FAU - Fuentes-Panana, Ezequiel M
AU  - Fuentes-Panana EM
AD  - Unidad de Investigacion en Virologia y Cancer, Hospital Infantil de Mexico 
      Federico Gomez, Mexico City, Mexico.
FAU - Wood, Christopher
AU  - Wood C
AUID- ORCID: 0000-0001-7175-7121
AD  - Laboratorio Nacional de Microscopia Avanzada, Universidad Nacional Autonoma de 
      Mexico, Cuernavaca, Morelos, Mexico.
FAU - Bonifaz, Laura C
AU  - Bonifaz LC
AUID- ORCID: 0000-0001-8482-5648
AD  - UMAE Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto 
      Mexicano del Seguro Social, Unidad de Investigacion Medica en Inmunoquimica, 
      Mexico City, Mexico.
AD  - Coordinacion de Investigacion en Salud, Centro Medico Nacional Siglo XXI, 
      Instituto Mexicano del Seguro Social, Mexico City, Mexico.
LA  - eng
PT  - Journal Article
DEP - 20221012
PL  - Egypt
TA  - J Oncol
JT  - Journal of oncology
JID - 101496537
PMC - PMC9581597
COIS- The authors declare that there are no conflicts of interest regarding the 
      publication of this paper.
EDAT- 2022/10/25 06:00
MHDA- 2022/10/25 06:01
PMCR- 2022/10/12
CRDT- 2022/10/24 04:14
PHST- 2022/05/18 00:00 [received]
PHST- 2022/07/29 00:00 [accepted]
PHST- 2022/10/24 04:14 [entrez]
PHST- 2022/10/25 06:00 [pubmed]
PHST- 2022/10/25 06:01 [medline]
PHST- 2022/10/12 00:00 [pmc-release]
AID - 10.1155/2022/9775736 [doi]
PST - epublish
SO  - J Oncol. 2022 Oct 12;2022:9775736. doi: 10.1155/2022/9775736. eCollection 2022.