Combining ICIs with immumomodulators: lessons from different metastatic sites

Hepatology ◽  
2022 ◽  
Author(s):  
Einat Cinnamon ◽  
Eli Pikarsky
Keyword(s):  
Metastatic Sites

201Tl Scintigraphy in the Evaluation of Palpable and Nonpalpable Breast Lesions: Correlation with Mammography and Ultrasonography

1997 ◽  
Vol 36 (08) ◽  
pp. 282-288 ◽  
Author(s):  
T. Atasever ◽  
A. Özdemir ◽  
I. Öznur ◽  
N. I. Karabacak ◽  
N. Gökçora ◽  
...  
Keyword(s):  
Final Diagnosis ◽  
Lower Sensitivity ◽  
Breast Lesions ◽  
Breast Cancers ◽  
Combined Use ◽  
Malignant Breast ◽  
Malignant Lesions ◽  
Benign Breast Lesions ◽  
Palpable Breast ◽  
Metastatic Sites

Summary Aim: Our goal was to determine the clinical usefulness of TI-201 to identify breast cancer in patients with suspicious breast lesions on clinical examination, and/or abnormal radiologic (mammography and/or ultrasonography) findings. Methods: TI-201 scintigraphy were performed in sixty-eight patients with 70 breast abnormalities (51 palpable, 19 nonpalpable) and compared with mammography and ultrasonography (US). Early (15 min) and late (3 h) images of the breasts were obtained following the injection of 111 MBq (3 mCi) of TI-201. Visual and semiquantitative interpretation was performed. Results: Final diagnosis confirmed 52 malignant breast lesions and 18 benign conditions. TI-201 visualized 47 of 52 (90%) overall malignant lesions. Thirty-eight of 40 (95%) palpable and 9 of 12 (75%) nonpalpable breast cancers were detected by TI-201 scintigraphy. The smallest mass lesion detected by TI-201 measured 1.5x1.0 cm. Eleven breast lesions were interpreted as indeterminate by mammography and/or sonography. TI-201 scintigraphy excluded malignancy in 7 of 8 (88%) patients with benign breast lesions interpreted as indeterminate. Five of the 18 (28%) benign breast lesions showed TI-201 uptake. None of the fibroadenoma and fibrocystic changes accumulated TI-201. TI-201 scintigraphy, mammography and ultrasonography showed 90%, 92%, 85% overall sensitivity and 72%, 56%, 61% overall specificity respectively. Twenty-one of the 28 (75%) axillary nodal metastatic sites were also detected by TI-201. In malignant and benign lesions, early and late lesion/contralateral normal side (L/N) ratios were 1.58 ± 0.38 (mean ± SD) and 1.48 ± 0.32 (p >0.05), 1.87 ± 0.65 and 1.34 ± 0.20 (p<0.05) respectively. The mean early and late L/N ratios of malignant and benign groups did not show statistical difference (p>0.05). Conclusion: Overall, TI-201 scintigraphy was the most specific of the three methods and yielded favourable results in palpable breast cancers, while it showed lower sensitivity in nonpalpable cancers and axillary metastases. Combined use of TI-201 scintigraphy with mammography and US seems to be useful in difficult cases, such as dense breasts and indeterminate breast lesions.

scholarly journals New insights in the expression of stromal caveolin 1 in breast cancer spread to axillary lymph nodes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cristian Scatena ◽  
Giovanni Fanelli ◽  
Giuseppe Nicolò Fanelli ◽  
Michele Menicagli ◽  
Paolo Aretini ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Cancer Metastasis ◽  
Tumor Stroma ◽  
Disease Recurrence ◽  
Metastatic Spread ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Axillary Lymph Node Metastases ◽  
Stromal Compartment ◽  
Metastatic Sites

AbstractRecent evidence suggests that a loss of expression of caveolin in the stromal compartment (sCav-1) of human invasive breast carcinoma (IBC) may be a predictor of disease recurrence, metastasis and poor outcome. At present, there is little knowledge regarding the expression of sCav-1 at the metastatic sites. We therefore studied sCav-1 expression in IBCs and in their axillary lymph nodes to seek a correlation with cancer metastasis. 189 consecutive invasive IBCs (53 with axillary lymph node metastases and 136 without) were studied by immunohistochemistry, using a rabbit polyclonal anti-Cav-1 antibody. In IBCs sCav-1 was evaluated in fibroblasts scattered in the tumor stroma whereas in lymph nodes sCav-1 was assessed in fibroblast-like stromal cells. For the first time, we observed a statistically significant progressive loss of sCav-1 from normal/reactive axillary lymph nodes of tumors limited to the breast to metastatic axillary lymph nodes, through normal/reactive axillary lymph nodes of tumors with axillary metastatic spread. These data indicate that Cav-1 expressed by the stromal compartment of lymph nodes, somehow, may possibly contribute to metastatic spread in IBC.

scholarly journals No Impact of NRAS Mutation on Features of Primary and Metastatic Melanoma or on Outcomes of Checkpoint Inhibitor Immunotherapy: An Italian Melanoma Intergroup (IMI) Study

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 475
Author(s):  
Michele Guida ◽  
Nicola Bartolomeo ◽  
Pietro Quaglino ◽  
Gabriele Madonna ◽  
Jacopo Pigozzo ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Checkpoint Inhibitor ◽  
Progression Free Survival ◽  
Nras Mutation ◽  
Disease Free Interval ◽  
Free Survival ◽  
Mutational Status ◽  
Metastatic Sites ◽  
Disease Free ◽  
Mutant Braf

Aims: It is debated whether the NRAS-mutant melanoma is more aggressive than NRAS wildtype. It is equally controversial whether NRAS-mutant metastatic melanoma (MM) is more responsive to checkpoint inhibitor immunotherapy (CII). 331 patients treated with CII as first-line were retrospectively recruited: 162 NRAS-mutant/BRAF wild-type (mut/wt) and 169 wt/wt. We compared the two cohorts regarding the characteristics of primary and metastatic disease, disease-free interval (DFI) and outcome to CII. No substantial differences were observed between the two groups at melanoma onset, except for a more frequent ulceration in the wt/wt group (p = 0.03). Also, the DFI was very similar in the two cohorts. In advanced disease, we only found lung and brain progression more frequent in the wt/wt group. Regarding the outcomes to CII, no significant differences were reported in overall response rate (ORR), disease control rate (DCR), progression free survival (PFS) or overall survival (OS) (42% versus 37%, 60% versus 59%, 12 (95% CI, 7–18) versus 9 months (95% CI, 6–16) and 32 (95% CI, 23–49) versus 27 months (95% CI, 16–35), respectively). Irrespectively of mutational status, a longer OS was significantly associated with normal LDH, <3 metastatic sites, lower white blood cell and platelet count, lower neutrophil-to-lymphocyte (N/L) ratio. Our data do not show increased aggressiveness and higher responsiveness to CII in NRAS-mutant MM.

scholarly journals The cancer glycocalyx mediates intravascular adhesion and extravasation during metastatic dissemination

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Giovanni S. Offeddu ◽  
Cynthia Hajal ◽  
Colleen R. Foley ◽  
Zhengpeng Wan ◽  
Lina Ibrahim ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Vascular System ◽  
Migration And Invasion ◽  
Improve Patient Survival ◽  
Adhesive Interactions ◽  
Vitro Model ◽  
Metastatic Sites

AbstractThe glycocalyx on tumor cells has been recently identified as an important driver for cancer progression, possibly providing critical opportunities for treatment. Metastasis, in particular, is often the limiting step in the survival to cancer, yet our understanding of how tumor cells escape the vascular system to initiate metastatic sites remains limited. Using an in vitro model of the human microvasculature, we assess here the importance of the tumor and vascular glycocalyces during tumor cell extravasation. Through selective manipulation of individual components of the glycocalyx, we reveal a mechanism whereby tumor cells prepare an adhesive vascular niche by depositing components of the glycocalyx along the endothelium. Accumulated hyaluronic acid shed by tumor cells subsequently mediates adhesion to the endothelium via the glycoprotein CD44. Trans-endothelial migration and invasion into the stroma occurs through binding of the isoform CD44v to components of the sub-endothelial extra-cellular matrix. Targeting of the hyaluronic acid-CD44 glycocalyx complex results in significant reduction in the extravasation of tumor cells. These studies provide evidence of tumor cells repurposing the glycocalyx to promote adhesive interactions leading to cancer progression. Such glycocalyx-mediated mechanisms may be therapeutically targeted to hinder metastasis and improve patient survival.

scholarly journals Blocking Migration of Polymorphonuclear Myeloid-Derived Suppressor Cells Inhibits Mouse Melanoma Progression

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 726
Author(s):  
Christopher Groth ◽  
Ludovica Arpinati ◽  
Merav E. Shaul ◽  
Nina Winkler ◽  
Klara Diester ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Checkpoint Inhibitors ◽  
Suppressor Cells ◽  
Receptor Expression ◽  
Myeloid Derived Suppressor Cells ◽  
Melanoma Progression ◽  
Relative Contribution ◽  
Immunosuppressive Tumor Microenvironment ◽  
Metastatic Sites

Background: Despite recent improvement in the treatment of malignant melanoma by immune-checkpoint inhibitors, the disease can progress due to an immunosuppressive tumor microenvironment (TME) mainly represented by myeloid-derived suppressor cells (MDSC). However, the relative contribution of the polymorphonuclear (PMN) and monocytic (M) MDSC subsets to melanoma progression is not clear. Here, we compared both subsets regarding their immunosuppressive capacity and recruitment mechanisms. Furthermore, we inhibited PMN-MDSC migration in vivo to determine its effect on tumor progression. Methods: Using the RET transgenic melanoma mouse model, we investigated the immunosuppressive function of MDSC subsets and chemokine receptor expression on these cells. The effect of CXCR2 inhibition on PMN-MDSC migration and tumor progression was studied in RET transgenic mice and in C57BL/6 mice after surgical resection of primary melanomas. Results: Immunosuppressive capacity of intratumoral M- and PMN-MDSC was comparable in melanoma bearing mice. Anti-CXCR2 therapy prolonged survival of these mice and decreased the occurrence of distant metastasis. Furthermore, this therapy reduced the infiltration of melanoma lesions and pre-metastatic sites with PMN-MDSC that was associated with the accumulation of natural killer (NK) cells. Conclusions: We provide evidence for the tumor−promoting properties of PMN-MDSC as well as for the anti-tumor effects upon their targeting in melanoma bearing mice.

scholarly journals MO3-2 Prognostic significance of metastatic sites in recurrent or metastatic squamous cell carcinoma of the head and neck

2021 ◽  
Vol 32 ◽  
pp. S296
Author(s):  
Ari Nishimura ◽  
Tomoya Yokota ◽  
Yoshiyuki Iida ◽  
Tomoyuki Kamijo ◽  
Takashi Mukaigawa ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Prognostic Significance ◽  
Metastatic Squamous Cell Carcinoma ◽  
Metastatic Sites

scholarly journals Evaluation of Merkel Cell Polyomavirus DNA in Tissue Samples from Italian Patients with Diagnosis of MCC

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 61
Author(s):  
Carla Prezioso ◽  
Raffaella Carletti ◽  
Francisco Obregon ◽  
Francesca Piacentini ◽  
Anna Maria Manicone ◽  
...  
Keyword(s):  
Point Mutations ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell ◽  
Tissue Samples ◽  
Metastatic Lesions ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Metastatic Sites ◽  
Archived Specimens ◽  
Coding Control

Because the incidence of Merkel cell carcinoma (MCC) has increased significantly during the last 10 years and it is recognized that Merkel cell polyomavirus (MCPyV) and ultraviolet (UV) radiation represent two different etiological inputs sharing clinical, histopathological, and prognostic similar features, although with different prognosis, this study investigated the detection of MCPyV in skin and lymph nodes with histological diagnosis of MCC. Formalin-fixed paraffin-embedded tissue (FFPE) were retrieved from archived specimens and MCPyV non-coding control region (NCCR) and viral capsid protein 1 (VP1) sequences were amplified and sequenced. Results provide an interesting observation concerning the discrepancy between the MCPyV DNA status in primary and metastatic sites: in fact, in all cases in which primary and metastatic lesions were investigated, MCPyV DNA was detected only in the primary lesions. Our data further support the “hit-and-run” theory, also proposed by other authors, and may lead to speculation that in some MCCs the virus is only necessary for the process of tumor initiation and that further mutations may render the tumor independent from the virus. Few point mutations were detected in the NCCR and only silent mutations were observed in the VP1 sequence compared to the MCPyV MCC350 isolate. To unequivocally establish a role of MCPyV in malignancies, additional well-controlled investigations are required, and larger cohorts should be examined.

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