Regional immunotherapy for liver and peritoneal metastases

Reha, Jeffrey; Katz, Steven C.

doi:10.1002/jso.24641

Cited by 6 publications

(6 citation statements)

References 100 publications

(169 reference statements)

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“…Elucidating a method to enhance antitumor immunity and immunotherapy seems to be a challenge in PDAC treatment. Immune evasion and T cell dysfunction can be mediated by a variety of mechanisms, such as the immunosuppressive microenvironment in PDAC patients, which involves interactions among tumor cells, infiltrated immune cells and stromal components [ 108 , 117 ], and makes a major hurdle for immune responses [ 133 ]. As a currently compelling role, PSCs display multiple effects on immunosuppressive regulation that makes PDAC therapeutics more difficult [ 134 , 135 ] (Fig.…”

Section: Introductionmentioning

confidence: 99%

The critical roles of activated stellate cells-mediated paracrine signaling, metabolism and onco-immunology in pancreatic ductal adenocarcinoma

et al. 2018

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant diseases worldwide. It is refractory to conventional treatments, and consequently has a documented 5-year survival rate as low as 7%. Increasing evidence indicates that activated pancreatic stellate cells (PSCs), one of the stromal components in tumor microenvironment (TME), play a crucial part in the desmoplasia, carcinogenesis, aggressiveness, metastasis associated with PDAC. Despite the current understanding of PSCs as a “partner in crime” to PDAC, detailed regulatory roles of PSCs and related microenvironment remain obscure. In addition to multiple paracrine signaling pathways, recent research has confirmed that PSCs-mediated tumor microenvironment may influence behaviors of PDAC via diverse mechanisms, such as rewiring metabolic networks, suppressing immune responses. These new activities are closely linked with treatment and prognosis of PDAC. In this review, we discuss the recent advances regarding new functions of activated PSCs, including PSCs-cancer cells interaction, mechanisms involved in immunosuppressive regulation, and metabolic reprogramming. It’s clear that these updated experimental or clinical studies of PSCs may provide a promising approach for PDAC treatment in the near future.

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Section: Introductionmentioning

confidence: 99%

The critical roles of activated stellate cells-mediated paracrine signaling, metabolism and onco-immunology in pancreatic ductal adenocarcinoma

et al. 2018

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“…Peritoneal metastases of ovarian, pancreatic, gastric, and colon cancers are common, and in most cases are of poor prognosis and survival rate if left untreated(48)(49)(50)(51).Targeting and treatment of peritoneal tumors remain a challenge due to delivery, pharmacology, and efficacy(51). Regional chimeric antigen receptor (CAR) T-cell infusion for peritoneal carcinomatosis has shown to be effective, suggesting that the regional activation of T cells is important in clearing of tumors in the peritoneum(52,53).It would be of interest to test in different models of peritoneal tumors whether targeting SLAMF6 could play a role in clearing these tumors.Overall, besides the ability of anti-SLAMF6 to induce ADCC, improvement in effector CD8 + T-cell responses makes SLAMF6 an intriguing candidate for therapy as it appears to not only work on tumors in secondary lymphoid organs and the peripheral blood but also in hypoxic niches like the PerC or in solid tumors.…”

mentioning

confidence: 99%

SLAMF6 as a Regulator of Exhausted CD8+ T Cells in Cancer

Yigit

Wang

Hacken

et al. 2019

Cancer Immunology Research

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The tumor microenvironment in leukemia and solid tumors induces a shift of activated CD8 + cytotoxic T cells to an exhausted state, characterized by loss of proliferative capacity and impaired immunologic synapse formation. Efficient strategies and targets need to be identified to overcome T-cell exhaustion and further improve overall responses in the clinic. Here, we took advantage of the E-TCL1 chronic lymphocytic leukemia (CLL) and B16 melanoma mouse models to assess the role of the homophilic cell surface receptor SLAMF6 as an immune checkpoint regulator. The transfer of SLAMF6 + E-TCL1 cells into SLAMF6-/recipients, in contrast to wild-type (WT) recipients, significantly induced expansion of a PD-1 + subpopulation among CD3 + CD44 + CD8 + T cells, which had impaired cytotoxic functions. Conversely, administering anti-SLAMF6 significantly reduced the leukemic burden in E-TCL1 recipient WT mice concomitantly with a loss of PD-1 + CD3 + CD44 + CD8 + T cells with significantly increased effector functions. Anti-SLAMF6 significantly reduced leukemic burden in the peritoneal cavity, a niche where antibody-dependent cellular cytotoxicity (ADCC) is impaired, possibly through activation of CD8 + T cells. Targeting of SLAMF6 not only impacted tumor growth in B cell-related leukemia and lymphomas but also nonhematopoietic tumors like B16 melanoma, where SLAMF6 is not expressed. In vitro exhausted CD8 + T cells showed increased degranulation when anti-human SLAMF6 was added in culture. Taken together, anti-SLAMF6 both effectively corrected CD8 + Tcell dysfunction and had a direct effect on tumor progression. The outcomes of our studies suggest that targeting SLAMF6 is a potential therapeutic strategy.

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“…The first whole-cell vaccine was GVAX, which has GM-CSF. GVAX has been evaluated in metastatic CRC patients with or without chemotherapy showing an overall survival of 2.3 and 4.3 months with less toxic effects than conventional treatment [126]. Gene therapy has been applied for immunotherapy as encapsulation and delivery of plasmids DNA (pDNAs).…”

Section: Immune Checkpointmentioning

confidence: 99%

Therapeutic Approaches for Metastases from Colorectal Cancer and Pancreatic Ductal Carcinoma

et al. 2021

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Metastasis is the process of dissemination of a tumor, whereby cells from the primary site dislodge and find their way to other tissues where secondary tumors establish. Metastasis is the primary cause of death related to cancer. This process warrants changes in original tumoral cells and their microenvironment to establish a metastatic niche. Traditionally, cancer therapy has focused on metastasis prevention by systematic treatments or direct surgical re-sectioning. However, metastasis can still occur. More recently, new therapies direct their attention to targeting cancer stem cells. As they propose, these cells could be the orchestrators of the metastatic niche. In this review, we describe conventional and novel developments in cancer therapeutics for liver and lung metastasis. We further discuss the resistance mechanisms of targeted therapy, the advantages, and disadvantages of diverse treatment approaches, and future novel strategies to enhance cancer prognosis.

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Regional immunotherapy for liver and peritoneal metastases

Cited by 6 publications

References 100 publications

The critical roles of activated stellate cells-mediated paracrine signaling, metabolism and onco-immunology in pancreatic ductal adenocarcinoma

The critical roles of activated stellate cells-mediated paracrine signaling, metabolism and onco-immunology in pancreatic ductal adenocarcinoma

SLAMF6 as a Regulator of Exhausted CD8+ T Cells in Cancer

Therapeutic Approaches for Metastases from Colorectal Cancer and Pancreatic Ductal Carcinoma

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