Characterization of the intra-prostatic immune cell infiltration in androgen-deprived prostate cancer patients

Gannon, Philippe O.; Poisson, Alexis; Delvoye, Nathalie; Lapointe, Réjean; Mes-Masson, Anne-Marie; Saad, Fred

doi:10.1016/j.jim.2009.06.004

Cited by 228 publications

(214 citation statements)

References 33 publications

Supporting

Mentioning

199

Contrasting

Unclassified

Order By: Relevance

“…Specifically, we used the pixel count algorithm (ImageScope™, Aperio) for large-scale quantification of lymphatics, lymphocytes and immune suppressive molecules. Pixel-based analysis has been validated as an accurate strategy for the assessment of cell density in tissue sections, 48 and may be more precise than cell-counting algorithms, especially in the setting of dense and relatively homogenous cell populations such as within the tumor mass.…”

Section: Discussionmentioning

confidence: 99%

“…The resulting high-resolution digital images were analyzed with the ImageScope™ software, version 12.1 (Aperio Technologies, Vista, CA, USA), using the pixel positive cell algorithm 9.1 as previously described and validated. 48 Briefly, this algorithm detects pixels that match input parameters set for the algorithm and generates four output values based on the pixel's color range: haematoxylin or negative signal (blue in mark-up image), weak positive (yellow in mark-up image), positive (orange in mark-up image) and strong positive (brown in mark-up image) (Fig. S7).…”

Section: Staining Quantificationmentioning

confidence: 99%

See 1 more Smart Citation

Lymphatic vessel density is associated with CD8⁺ T cell infiltration and immunosuppressive factors in human melanoma

et al. 2018

Self Cite

View full text Add to dashboard Cite

Increased density of tumor-associated lymphatic vessels correlates with poor patient survival in melanoma and other cancers, yet lymphatic drainage is essential for initiating an immune response. Here we asked whether and how lymphatic vessel density (LVD) correlates with immune cell infiltration in primary tumors and lymph nodes (LNs) from patients with cutaneous melanoma. Using immunohistochemistry and quantitative image analysis, we found significant positive correlations between LVD and CD8+ T cell infiltration as well as expression of the immunosuppressive molecules inducible nitric oxide synthase (iNOS) and 2,3-dioxygénase (IDO). Interestingly, similar associations were seen in tumor-free LNs adjacent to metastatic ones, indicating loco-regional effects of tumors. Our data suggest that lymphatic vessels play multiple roles at tumor sites and LNs, promoting both T cell infiltration and adaptive immunosuppressive mechanisms. Lymph vessel associated T cell infiltration may increase immunotherapy success rates provided that the treatment overcomes adaptive immune resistance.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Staining Quantificationmentioning

confidence: 99%

Lymphatic vessel density is associated with CD8⁺ T cell infiltration and immunosuppressive factors in human melanoma

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…In majority of the studies, high numbers of immune cells, such as natural killer (NK) cells or CD8+T cells, infiltrating the tumors have been shown to correlate with an improved prognosis for cancer patients (Coca et al, 1997;Deschoolmeester et al, 2010). Elevated CD56+NK cell count has been reported to be associated with a lower risk of progression in prostate cancer (Gannon et al, 2009), and with poor patient outcome in renal cell carcinoma (Daniel et al, 2003). In the present study, analysis of response to treatment and survival, using log rank test after a 4 year follow up period, showed that the patients with low CD56 intratumoral count had better survival than high CD56 intratumoral count (χ2=4.80, p<0.05), with 0.52 fold lower death rate as compared to patients with high CD56 intratumoral count (HR=0.52, 95% CI=0.28-0.93).…”

Section: Discussionmentioning

confidence: 99%

Is the Tumor Infiltrating Natural Killer Cell (NK-TILs) Count in Infiltrating Ductal Carcinoma of Breast Prognostically Significant?

Rathore

Goel²,

Makker³

et al. 2014

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Asian Pac J Cancer Prev, 15 (8), 3757-3761 IntroductionBreast cancer is the most common cause of cancer death in women worldwide (Key et al., 2001), and represents the leading or second most leading cancer in females in India (Ferlay et al., 2010;D'Souza et al., 2013a;2013b). Currently, two major challenges of breast cancer research are; to understand the interrelation between breast cancer and anti-tumor immunity, and to identify candidates whose targeting would contribute to enhance anti-tumor efficiency (Mamessier et al., 2012).The cancer tissue is invaded by a mixed population of immune cells, including T-cells, B-cells, natural killer (NK) cells and macrophages. For a long time NK cells were considered merely as relatively primitive killers, but now they are seen not only as bonafide actors in innate immunity but are also important cells that shape and influence the adaptive immune responses (Poli et al., 2009). NK cells are effector lymphocytes of innate immune system that act by limiting the growth and dissemination of the tumor and are known to have an immunoregulatory role.An established marker for NK cells, CD56, is an AbstractPurpose: The aim of this study was to investigate the prognostic significance of the CD56+NK-TIL count in infiltrating ductal carcinoma (IDC) of breast. Material and Methods: Immunohistochemistry (IHC) was performed using antibodies specific for CD56 on formalin-fixed and paraffin-embedded tissue sections of 175 infiltrating ductal carcinomas (IDC) of breast. Distribution of intratumoral and stromal CD56+NK-TILs was assessed semi-quantitatively. Results: A low intratumoral CD56+count showed significant and inverse associations with tumor grade, stage, and lymph node status, whereas it had significant and direct association with response to treatment indicating good prognosis. These patients had better survival (χ 2 =4.80, p<0.05) and 0.52 fold lower death rate (HR=0.52, 95% CI=0.28-0.93) as compared to patients with high CD56+ intratumoral count. The association of survival was insignificant with low CD56 stromal count as compared to high CD56 stromal count (χ 2 =1.60, p>0.05). Conclusion: To conclude, although NK-TIL count appeared as a significant predictor of prognosis, it alone may not be sufficient for predicting the outcome considering the fact that there exists a crosstalk between NK-TILs and the other immune infiltrating TILs.

show abstract

“…Hence, there remains a need to improve outcomes in these patients. ADT has been shown to augment antitumor immune responses in animal models (5-7) and in patients with prostate cancer (6,(8)(9)(10), especially when combined with immunotherapies (11). Several (but not all) studies have shown superior immunologic and antitumor responses when immunotherapy was administered prior to ADT (7,12,13).…”

Section: Introductionmentioning

confidence: 99%

Sequencing of Sipuleucel-T and Androgen Deprivation Therapy in Men with Hormone-Sensitive Biochemically Recurrent Prostate Cancer: A Phase II Randomized Trial

Investigators

2017

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: STAND, a randomized, phase II, open-label trial (NCT01431391), assessed sequencing of sipuleucel-T (an autologous cellular immunotherapy) with androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BRPC) patients at high risk for metastasis.Experimental Design: Men with BRPC following prostatectomy and/or radiotherapy, a PSA doubling time 12 months, and no metastasis were enrolled. Patients were randomized (34/arm) to sipuleucel-T followed by ADT (started 2 weeks after sipuleucel-T completion), or ADT followed by sipuleucel-T (started 12 weeks after ADT initiation); ADT continued for 12 months in both arms. The primary endpoint was PA2024-specific T-cell response [enzyme-linked immunospot (ELISPOT)] over time.Results: PA2024-specific ELISPOT responses over time were similar between groups, except at week 6, where responses were higher with sipuleucel-T!ADT versus ADT!sipuleucel-T (P ¼ 0.013). PA2024-specific T-cell proliferation responses, averaged across time points, were approximately 2-fold higher with sipuleucel-T!ADT versus ADT!sipuleucel-T (P ¼ 0.001). PA2024-specific cellular and humoral responses and prostatic acid phosphatase-specific humoral responses increased significantly versus baseline (P < 0.001) and were maintained for 24 months (both arms). Median time-to-PSA recurrence was similar between arms (21.8 vs. 22.6 months, P ¼ 0.357). Development of a PA2024-specific humoral response correlated with prolonged time-to-PSA progression (HR, 0.22; 95% CI, 0.08-0.67; P ¼ 0.007). Sipuleucel-T with ADT was generally well tolerated.Conclusions: Sipuleucel-T!ADT appears to induce greater antitumor immune responses than the reverse sequence. These results warrant further investigation to determine whether this sequence leads to improved clinical outcomes, as well as the independent contribution of ADT alone in terms of immune activation.

show abstract

Characterization of the intra-prostatic immune cell infiltration in androgen-deprived prostate cancer patients

Cited by 228 publications

References 33 publications

Lymphatic vessel density is associated with CD8⁺ T cell infiltration and immunosuppressive factors in human melanoma

Lymphatic vessel density is associated with CD8⁺ T cell infiltration and immunosuppressive factors in human melanoma

Is the Tumor Infiltrating Natural Killer Cell (NK-TILs) Count in Infiltrating Ductal Carcinoma of Breast Prognostically Significant?

Sequencing of Sipuleucel-T and Androgen Deprivation Therapy in Men with Hormone-Sensitive Biochemically Recurrent Prostate Cancer: A Phase II Randomized Trial

Contact Info

Product

Resources

About

Characterization of the intra-prostatic immune cell infiltration in androgen-deprived prostate cancer patients

Cited by 228 publications

References 33 publications

Lymphatic vessel density is associated with CD8+ T cell infiltration and immunosuppressive factors in human melanoma

Lymphatic vessel density is associated with CD8+ T cell infiltration and immunosuppressive factors in human melanoma

Is the Tumor Infiltrating Natural Killer Cell (NK-TILs) Count in Infiltrating Ductal Carcinoma of Breast Prognostically Significant?

Sequencing of Sipuleucel-T and Androgen Deprivation Therapy in Men with Hormone-Sensitive Biochemically Recurrent Prostate Cancer: A Phase II Randomized Trial

Contact Info

Product

Resources

About

Lymphatic vessel density is associated with CD8⁺ T cell infiltration and immunosuppressive factors in human melanoma

Lymphatic vessel density is associated with CD8⁺ T cell infiltration and immunosuppressive factors in human melanoma