PMID- 22261803
OWN - NLM
STAT- MEDLINE
DCOM- 20120626
LR  - 20210103
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 18
IP  - 5
DP  - 2012 Mar 1
TI  - Infiltration of Lynch colorectal cancers by activated immune cells associates 
      with early staging of the primary tumor and absence of lymph node metastases.
PG  - 1237-45
LID - 10.1158/1078-0432.CCR-11-1997 [doi]
AB  - PURPOSE: Lynch syndrome colorectal cancers often lose human leukocyte antigen 
      (HLA) class I expression. The outgrowth of clones with immune evasive phenotypes 
      is thought to be positively selected by the action of cytotoxic T cells that 
      target HLA class I-positive cancer cells. To investigate this hypothesis, we 
      related the type and density of tumor lymphocytic infiltrate in Lynch colorectal 
      cancers with their HLA class I phenotype and clinicopathologic stage. 
      EXPERIMENTAL DESIGN: HLA class I expression was assessed by means of 
      immunohistochemistry. Characterization of tumor-infiltrating lymphocytes was 
      carried out by using a triple immunofluorescence procedure that allowed the 
      simultaneous detection of CD3-, CD8-, and granzyme B (GZMB)-positive cells. 
      Additional markers were also used for further characterization of an elusive 
      CD3(-)/CD8(-)/GZMB(+) cell population. RESULTS: We discovered that high tumor 
      infiltration by activated CD8(+) T cells correlated with aberrant HLA class I 
      expression and associated with early tumor stages (P < 0.05). CD8(+) T cells were 
      most abundant in HLA class I heterogeneous tumors (P = 0.02) and frequent in HLA 
      class I-negative cases (P = 0.04) when compared with HLA class I-positive 
      carcinomas. An elusive immune cell population (CD45(+)/CD8(-)/CD56(-)/GZMB(+)) 
      was characteristic for HLA class I-negative tumors lacking lymph node metastases 
      (P < 0.01). CONCLUSIONS: The immune system assumes an important role in 
      counteracting the progression of Lynch colorectal cancers and in selecting 
      abnormal HLA class I phenotypes. Our findings support the development of clinical 
      strategies that explore the natural antitumor immune responses occurring in Lynch 
      syndrome carriers.
FAU - de Miranda, Noel F C C
AU  - de Miranda NF
AD  - Department of Pathology, Leiden University Medical Centre, Leiden, The 
      Netherlands.
FAU - Goudkade, Danny
AU  - Goudkade D
FAU - Jordanova, Ekaterina S
AU  - Jordanova ES
FAU - Tops, Carli M J
AU  - Tops CM
FAU - Hes, Frederik J
AU  - Hes FJ
FAU - Vasen, Hans F A
AU  - Vasen HF
FAU - van Wezel, Tom
AU  - van Wezel T
FAU - Morreau, Hans
AU  - Morreau H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120118
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Histocompatibility Antigens Class I)
RN  - EC 3.4.21.- (GZMB protein, human)
RN  - EC 3.4.21.- (Granzymes)
SB  - IM
MH  - CD8-Positive T-Lymphocytes/immunology/metabolism
MH  - Colorectal Neoplasms, Hereditary Nonpolyposis/*immunology/metabolism/*pathology
MH  - Granzymes/metabolism
MH  - Histocompatibility Antigens Class I/immunology/metabolism
MH  - Humans
MH  - Immunophenotyping
MH  - Lymphatic Metastasis
MH  - Lymphocytes, Tumor-Infiltrating/*immunology/metabolism
MH  - Neoplasm Staging
MH  - Phenotype
MH  - T-Lymphocyte Subsets/immunology/metabolism
EDAT- 2012/01/21 06:00
MHDA- 2012/06/27 06:00
CRDT- 2012/01/21 06:00
PHST- 2012/01/21 06:00 [entrez]
PHST- 2012/01/21 06:00 [pubmed]
PHST- 2012/06/27 06:00 [medline]
AID - 1078-0432.CCR-11-1997 [pii]
AID - 10.1158/1078-0432.CCR-11-1997 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2012 Mar 1;18(5):1237-45. doi: 10.1158/1078-0432.CCR-11-1997. 
      Epub 2012 Jan 18.