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Peripheral myeloid-derived suppressor and T regulatory PD-1 positive cells predict response to neoadjuvant short-course radiotherapy in rectal cancer patients.

Napolitano M, D'Alterio C, Cardone E, Trotta AM, Pecori B, Rega D, Pace U, Scala D, Scognamiglio G, Tatangelo F, Cacciapuoti C, Pacelli R, Delrio P, Scala S - Oncotarget (2015)

Bottom Line: Peripheral Granulocytic-MDSCs (G-MDSC) [LIN-/HLA-DR-/CD11b+/CD14-/CD15+/CD33+], Monocytic (M-MDSC) [CD14+/HLA-DR-/lowCD11b+/CD33+] and Tregs [CD4+/CD25hi+/FOXP3+- CTLA-4/PD1] basal value was significantly higher in LARC patients compared to healthy donors (HD).In this pilot study MDSCs and Tregs decrease during the SC-RT treatment could represent a biomarker of response in LARC patients.Further studies are needed to confirm that the deepest M-MDSC reduction and increase in Treg-PD1 cells within 5-8 weeks from the beginning of treatment could discriminate LARC patients poor responding to SC-RT.

View Article: PubMed Central - PubMed

Affiliation: Immunology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - I.R.C.C.S., Naples, Italy.

ABSTRACT
Short-course preoperative radiotherapy (SC-RT) followed by total mesorectal excision (TME) is one therapeutic option for locally advanced rectal cancer (LARC) patients. Since radio-induced DNA damage may affect tumor immunogenicity, Myeloid-derived suppressor cells (MDSCs) and T regulatory cells (Tregs) were evaluated in 13 patients undergoing SC-RT and TME for LARC. Peripheral Granulocytic-MDSCs (G-MDSC) [LIN-/HLA-DR-/CD11b+/CD14-/CD15+/CD33+], Monocytic (M-MDSC) [CD14+/HLA-DR-/lowCD11b+/CD33+] and Tregs [CD4+/CD25hi+/FOXP3+- CTLA-4/PD1] basal value was significantly higher in LARC patients compared to healthy donors (HD). Peripheral MDSC and Tregs were evaluated at time 0 (T0), after 2 and 5 weeks (T2-T5) from radiotherapy; before surgery (T8) and 6-12 months after surgery (T9, T10). G-MDSC decreased at T5 and further at T8 while M-MDSC cells decreased at T5; Tregs reached the lowest value at T5. LARC poor responder patients displayed a major decrease in M-MDSC after SC-RT and an increase of Treg-PD-1. In this pilot study MDSCs and Tregs decrease during the SC-RT treatment could represent a biomarker of response in LARC patients. Further studies are needed to confirm that the deepest M-MDSC reduction and increase in Treg-PD1 cells within 5-8 weeks from the beginning of treatment could discriminate LARC patients poor responding to SC-RT.

No MeSH data available.


Related in: MedlinePlus

MDSC and Tregs cells infiltrated post treatment rectal cancerCD11b and FoxP3 immunohistochemical staining were conducted to reveal respectively MDSCs and Tregs tumor infiltrating cells. (A). Left panel: Number of infiltrating cells/HPF in good responder (blue line) versus poor responder (red line) patients shown as box and whisker plots: boxes extend from the 25th to the 75th percentile, with a colored line at the population; median; p < 0,05 value. Right panel: Representative tissue staining for CD11b and FoxP3 in good responder (blue line) and poor responder (red line) patients (Magnification 200X). (B). Left panel: Number of infiltrating cells/HPF in tumors with infiltrative margin (tumor budding) (red line) and tumors with “well-circumscribed” margin (blue line) shown as box and whisker plots: boxes extend from the 25th to the 75th percentile, with a colored line at the population; median; p < 0,05 value. Right panel: Representative tissue staining for CD11b and FoxP3 in tumors with infiltrative margin tumors (tumor budding) (red line) and well-circumscribed” (blue line) margin tumors patients (Magnification 200X).
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Figure 6: MDSC and Tregs cells infiltrated post treatment rectal cancerCD11b and FoxP3 immunohistochemical staining were conducted to reveal respectively MDSCs and Tregs tumor infiltrating cells. (A). Left panel: Number of infiltrating cells/HPF in good responder (blue line) versus poor responder (red line) patients shown as box and whisker plots: boxes extend from the 25th to the 75th percentile, with a colored line at the population; median; p < 0,05 value. Right panel: Representative tissue staining for CD11b and FoxP3 in good responder (blue line) and poor responder (red line) patients (Magnification 200X). (B). Left panel: Number of infiltrating cells/HPF in tumors with infiltrative margin (tumor budding) (red line) and tumors with “well-circumscribed” margin (blue line) shown as box and whisker plots: boxes extend from the 25th to the 75th percentile, with a colored line at the population; median; p < 0,05 value. Right panel: Representative tissue staining for CD11b and FoxP3 in tumors with infiltrative margin tumors (tumor budding) (red line) and well-circumscribed” (blue line) margin tumors patients (Magnification 200X).

Mentions: To correlate the peripheral MDSCs and Tregs with the primary tumour, CD11b [24, 25] and FOXP3 were evaluated on the surgical specimens (Supplementary Table 1). Increased staining for CD11b and FOXP3 was detected in poor responder patients compared to good responders (Figure 6A–6B; see Supplementary Figure 2) [21, 26], specifically in island of tumor budding, a rectal cancer poor prognostic factor [27] (Figure 6B). These results suggest that the peripheral evaluation of MDSCs and Tregs might correlate with the SC-RT tumor response.


Peripheral myeloid-derived suppressor and T regulatory PD-1 positive cells predict response to neoadjuvant short-course radiotherapy in rectal cancer patients.

Napolitano M, D'Alterio C, Cardone E, Trotta AM, Pecori B, Rega D, Pace U, Scala D, Scognamiglio G, Tatangelo F, Cacciapuoti C, Pacelli R, Delrio P, Scala S - Oncotarget (2015)

MDSC and Tregs cells infiltrated post treatment rectal cancerCD11b and FoxP3 immunohistochemical staining were conducted to reveal respectively MDSCs and Tregs tumor infiltrating cells. (A). Left panel: Number of infiltrating cells/HPF in good responder (blue line) versus poor responder (red line) patients shown as box and whisker plots: boxes extend from the 25th to the 75th percentile, with a colored line at the population; median; p < 0,05 value. Right panel: Representative tissue staining for CD11b and FoxP3 in good responder (blue line) and poor responder (red line) patients (Magnification 200X). (B). Left panel: Number of infiltrating cells/HPF in tumors with infiltrative margin (tumor budding) (red line) and tumors with “well-circumscribed” margin (blue line) shown as box and whisker plots: boxes extend from the 25th to the 75th percentile, with a colored line at the population; median; p < 0,05 value. Right panel: Representative tissue staining for CD11b and FoxP3 in tumors with infiltrative margin tumors (tumor budding) (red line) and well-circumscribed” (blue line) margin tumors patients (Magnification 200X).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4480750&req=5

Figure 6: MDSC and Tregs cells infiltrated post treatment rectal cancerCD11b and FoxP3 immunohistochemical staining were conducted to reveal respectively MDSCs and Tregs tumor infiltrating cells. (A). Left panel: Number of infiltrating cells/HPF in good responder (blue line) versus poor responder (red line) patients shown as box and whisker plots: boxes extend from the 25th to the 75th percentile, with a colored line at the population; median; p < 0,05 value. Right panel: Representative tissue staining for CD11b and FoxP3 in good responder (blue line) and poor responder (red line) patients (Magnification 200X). (B). Left panel: Number of infiltrating cells/HPF in tumors with infiltrative margin (tumor budding) (red line) and tumors with “well-circumscribed” margin (blue line) shown as box and whisker plots: boxes extend from the 25th to the 75th percentile, with a colored line at the population; median; p < 0,05 value. Right panel: Representative tissue staining for CD11b and FoxP3 in tumors with infiltrative margin tumors (tumor budding) (red line) and well-circumscribed” (blue line) margin tumors patients (Magnification 200X).
Mentions: To correlate the peripheral MDSCs and Tregs with the primary tumour, CD11b [24, 25] and FOXP3 were evaluated on the surgical specimens (Supplementary Table 1). Increased staining for CD11b and FOXP3 was detected in poor responder patients compared to good responders (Figure 6A–6B; see Supplementary Figure 2) [21, 26], specifically in island of tumor budding, a rectal cancer poor prognostic factor [27] (Figure 6B). These results suggest that the peripheral evaluation of MDSCs and Tregs might correlate with the SC-RT tumor response.

Bottom Line: Peripheral Granulocytic-MDSCs (G-MDSC) [LIN-/HLA-DR-/CD11b+/CD14-/CD15+/CD33+], Monocytic (M-MDSC) [CD14+/HLA-DR-/lowCD11b+/CD33+] and Tregs [CD4+/CD25hi+/FOXP3+- CTLA-4/PD1] basal value was significantly higher in LARC patients compared to healthy donors (HD).In this pilot study MDSCs and Tregs decrease during the SC-RT treatment could represent a biomarker of response in LARC patients.Further studies are needed to confirm that the deepest M-MDSC reduction and increase in Treg-PD1 cells within 5-8 weeks from the beginning of treatment could discriminate LARC patients poor responding to SC-RT.

View Article: PubMed Central - PubMed

Affiliation: Immunology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - I.R.C.C.S., Naples, Italy.

ABSTRACT
Short-course preoperative radiotherapy (SC-RT) followed by total mesorectal excision (TME) is one therapeutic option for locally advanced rectal cancer (LARC) patients. Since radio-induced DNA damage may affect tumor immunogenicity, Myeloid-derived suppressor cells (MDSCs) and T regulatory cells (Tregs) were evaluated in 13 patients undergoing SC-RT and TME for LARC. Peripheral Granulocytic-MDSCs (G-MDSC) [LIN-/HLA-DR-/CD11b+/CD14-/CD15+/CD33+], Monocytic (M-MDSC) [CD14+/HLA-DR-/lowCD11b+/CD33+] and Tregs [CD4+/CD25hi+/FOXP3+- CTLA-4/PD1] basal value was significantly higher in LARC patients compared to healthy donors (HD). Peripheral MDSC and Tregs were evaluated at time 0 (T0), after 2 and 5 weeks (T2-T5) from radiotherapy; before surgery (T8) and 6-12 months after surgery (T9, T10). G-MDSC decreased at T5 and further at T8 while M-MDSC cells decreased at T5; Tregs reached the lowest value at T5. LARC poor responder patients displayed a major decrease in M-MDSC after SC-RT and an increase of Treg-PD-1. In this pilot study MDSCs and Tregs decrease during the SC-RT treatment could represent a biomarker of response in LARC patients. Further studies are needed to confirm that the deepest M-MDSC reduction and increase in Treg-PD1 cells within 5-8 weeks from the beginning of treatment could discriminate LARC patients poor responding to SC-RT.

No MeSH data available.


Related in: MedlinePlus