Implications of Hereditary Origin on the Immune Phenotype of Mismatch Repair-Deficient Cancers: Systematic Literature Review
Abstract
:1. Introduction
2. Methods
2.1. Systematic Literature Search
2.2. Statistical Analysis
3. Results
3.1. Outcome of the Systematic Literature Search
3.2. Immune Infiltration in Hereditary and Sporadic MSI CRCs
3.3. Immune Infiltration in Hereditary and Sporadic Pre-malignant Colorectal Lesions
3.4. Immune Infiltration in Hereditary and Sporadic ECs
3.5. Immune Evasion Mechanisms in Hereditary and Sporadic MSI CRCs
3.6. Response to Therapy in Hereditary and Sporadic MSI CRCs
3.7. Alternative Explanations for Differing Immune Phenotypes
4. Summary
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Sample Number | LS Status | Marker (Clone) | Positive Cell Counts | Analyzed Area | Counting Method | |||||
---|---|---|---|---|---|---|---|---|---|---|
Proven | Suspected | |||||||||
colorectal cancer | Hereditary MSI CRCs | Sporadic MSI CRCs | Hereditary MSI CRCs | Sporadic MSI CRCs | ||||||
Janikovits et al., 2018 [47] | n = 18 | n = 38 | x | CD3 (PS1) | 143.1 * | 92.5 | tumor epithelial | median of positive cells per 0.25 mm2 | ||
PD-1 (NAT105) | 31 * | 2.7 | ||||||||
Koornstra et al., 2009 [50] | n = 20 | n = 26 | x | x | CD8 (na) | 18.6 | 23.9 | tumor epithelial | mean of positive cells in 10 hpf (400 × magnification) | |
Shia et al., 2003 [48] | n = 30 | n = 35 | x | CD3 (na) | 65 * | 19 | tumor epithelial | median of positive cells in 10 hpf (=1.96 mm2) | ||
Surmann et al., 2015 [51] | n = 35 | n = 34 | n.a. | CD4 (IF6) | 53.4 | 68.9 | tumor epithelial | median of positive cells per 0.25 mm2 | ||
CD4 (IF6) | 119.4 | 141.2 | stromal | |||||||
Takemoto et al., 2004 [49] | n = 19 | n = 12 | x | CD3 (×100) | 165.4 | 153.2 | stromal | mean/median of positive cells per 250 µm2 | ||
CD4 (×20) | 91.2 | 84.7 | ||||||||
CD8 (×20) | 51.5 | 47.6 | ||||||||
no numbers for epithelial cells | ||||||||||
colorectal adenomas | Koornstra et al., 2009 [50] | Hereditary Colorectal Adenomas | Sporadic Colorectal Adenomas | Hereditary Colorectal Adenomas | Sporadic Colorectal Adenomas | |||||
n = 50 | n = 69 | x | CD8 (na) | 6.6 * | 3.9 | epithelial | mean of positive cells in 10 hpf (400 × magnification) | |||
endometrial cancer | hereditary MSI ECs | sporadic MSI ECs | hereditary MSI ECs | sporadic MSI ECs | ||||||
Pakish et al., 2017 [52] | n = 20 | n = 38 | x | CD3 (SP7) | 84.3 | 84.6 | stromal | median of positive cells per 1 mm2 | ||
CD4 (4B12) | 16.3 | 22.1 | ||||||||
CD8 (4B11) | 82.8 * | 34.2 | ||||||||
PD-L1 (E1L3N) | 289.3 | 297.9 | ||||||||
CD3 (SP7) | 18.7 | 30 | tumor epithelial | |||||||
CD4 (4B12) | 2.8 | 8.6 | ||||||||
CD8 (4B11) | 8.2 | 4.2 | ||||||||
PD-L1 (E1L3N) | 4.8 | 8.2 | ||||||||
Ramchander et al., 2020 [53] | n = 25 | n = 33 | x | CD3 (F7.2.38) | 590 | 617 | tumor center | mean of positive cells per 200 µm2 | ||
CD8 (C8/144B) | 291 | 233 | ||||||||
CD45RO (UCLH1) | 597 | 653 | ||||||||
FoxP3 (236A/E7) | 72 | 58 | ||||||||
PD-1 (NAT105) | 156 * | 108 | ||||||||
CD3 (F7.2.38) | 386 | 241 | invasive margin | |||||||
CD8 (C8/144B) | 287 * | 116 | ||||||||
CD45RO (UCLH1) | 548 * | 296 | ||||||||
FoxP3 (236A/E7) | 61 | 28 | ||||||||
PD-1 (NAT105) | 118 * | 49 |
HLA I-B2M Mutations | Colorectal MSI Adenomas | LS Status | ||||
---|---|---|---|---|---|---|
Hereditary MSI CRCs | Sporadic MSI CRCs | Proven | Suspected | |||
Clendenning et al., 2018 [72] | 17.1% (7/41) | 29% (20/69) | 0% (0/42) | x | x | |
Dierssen et al., 2006 [73] | 20% (15/75) | 3% (1/33) | x | x | ||
Janikovits et al., 2018 [47] | 50% (9/18) | 26.3% (10/38) | x | x | ||
Kloor et al., 2007 [12] | 36.4% (16/44) | 15.4% (4/26) | 15.8% (6/38) | x | ||
Total | 35.9% (47/131) | 26.7% (35/131) | 7.5% (6/80) | |||
95% CI | 0.2816 to 0.4440 | 0.1985 to 0.3491 | ||||
p-value | 0.1425 | |||||
HLA II-Mutations in CIITA and RFX5 | ||||||
CIITA | RFX5 | |||||
Hereditary MSI CRCs | Sporadic MSI CRCs | Hereditary MSI CRCs | Sporadic MSI CRCs | |||
Surmann et al., 2015 [51] | 8.9% (3/35) | 0% (0/34) | 14.3% (5/35) | 26.5% (9/34) | n.a. |
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Bohaumilitzky, L.; von Knebel Doeberitz, M.; Kloor, M.; Ahadova, A. Implications of Hereditary Origin on the Immune Phenotype of Mismatch Repair-Deficient Cancers: Systematic Literature Review. J. Clin. Med. 2020, 9, 1741. https://doi.org/10.3390/jcm9061741
Bohaumilitzky L, von Knebel Doeberitz M, Kloor M, Ahadova A. Implications of Hereditary Origin on the Immune Phenotype of Mismatch Repair-Deficient Cancers: Systematic Literature Review. Journal of Clinical Medicine. 2020; 9(6):1741. https://doi.org/10.3390/jcm9061741
Chicago/Turabian StyleBohaumilitzky, Lena, Magnus von Knebel Doeberitz, Matthias Kloor, and Aysel Ahadova. 2020. "Implications of Hereditary Origin on the Immune Phenotype of Mismatch Repair-Deficient Cancers: Systematic Literature Review" Journal of Clinical Medicine 9, no. 6: 1741. https://doi.org/10.3390/jcm9061741