scholarly journals CXCR6 governs the retention of tissue-resident memory T cells to promote enhanced surveillance and control of ovarian cancer

2020 ◽  
Author(s):  
Ravikumar Muthuswamy ◽  
AJ Robert McGray ◽  
Sebastiano Battaglia ◽  
Wenjun He ◽  
Anthony Miliotto ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Ovarian Tumor ◽  
Memory T Cells ◽  
Memory Cell ◽  
Tumor Control ◽  
Control Analysis ◽  
Resident Memory T Cells ◽  
And Control

AbstractWhile the beneficial role played by tissue-resident memory T cells (Trm) in tumor control has emerged, the chemotactic mechanisms associated with their localization and retention in the tumor microenvironment (TME) of cancers including ovarian are poorly understood. The current study has identified chemokine receptor CXCR6 as crucial for Trm responses to ovarian cancer by promoting their localization and retention in the ovarian tumor microenvironment. In human ovarian cancer patients, CXCR6 significantly marked CD8+ CD103+ tumor-infiltrating Trm cells. Functional studies in mice revealed high expression of CXCR6 in tumor-specific T cells that reside in tissues, but not by those in circulation. Knockout of CXCR6 in tumor-specific T cells led to a heightened circulatory response in blood, but diminished resident memory cell accumulation in tumors, culminating in poor tumor control. Analysis of Wild type (Wt.) and CXCR6KO (KO) tumor-specific T cells trafficking in recipient mice using bioluminescent imaging revealed that compared to Wt., KO T cells preferentially localized to the spleen, indicating the possibility of reduced retention in tumor tissues. These findings indicate that CXCR6 by mediating increased retention of tumor-specific T cells in the ovarian tumor microenvironment, promotes resident memory T cell-mediated surveillance and control of ovarian cancer.

scholarly journals Route of Immunization with Peptide-pulsed Dendritic Cells Controls the Distribution of Memory and Effector T Cells in Lymphoid Tissues and Determines the Pattern of Regional Tumor Control

2003 ◽  
Vol 198 (7) ◽  
pp. 1023-1034 ◽  
Author(s):  
David W. Mullins ◽  
Stacey L. Sheasley ◽  
Rebecca M. Ream ◽  
Timothy N.J. Bullock ◽  
Yang-Xin Fu ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Memory T Cells ◽  
Lung Metastases ◽  
Memory Cell ◽  
Lung Tumors ◽  
Tumor Control ◽  
Lymphoid Tissues ◽  
Memory Cd8 T Cells ◽  
And Control

We have established that the route of immunization with peptide-pulsed, activated DC leads to memory CD8+ T cells with distinct distributions in lymphoid tissues, which determines the ability to control tumors growing in different body sites. Both intravenous (i.v.) and subcutaneous (s.c.) immunization induced memory T cells in spleen and control of metastatic-like lung tumors. s.c. immunization also induced memory T cells in lymph nodes (LNs), imparting protection against subcutaneously growing tumors. In contrast, i.v. immunization-induced memory was restricted to spleen and failed to impart protective immunity against subcutaneously growing tumors. Memory cell distribution and tumor control were both linked to injection route–dependent localization of DCs in lymphoid compartments. Using peripheral LN–ablated mice, these LNs were shown to be essential for control of subcutaneously growing tumors but not lung metastases; in contrast, using immunized asplenic mice, we found that the spleen is necessary and sufficient for control of lung tumors, but unnecessary for control of subcutaneously growing tumors. These data demonstrate the existence of a previously undescribed population of splenic-resident memory CD8 T cells that are essential for the control of lung metastases. Thus, regional immunity based on memory T cell residence patterns is an important factor in DC-based tumor immunotherapy.

scholarly journals CXCR6 by increasing retention of memory CD8+ T cells in the ovarian tumor microenvironment promotes immunosurveillance and control of ovarian cancer

2021 ◽  
Vol 9 (10) ◽  
pp. e003329
Author(s):  
Ravikumar Muthuswamy ◽  
AJ Robert McGray ◽  
Sebastiano Battaglia ◽  
Wenjun He ◽  
Anthony Miliotto ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Cd8 T Cells ◽  
Ovarian Tumor ◽  
Critical Role ◽  
Peripheral Tissues ◽  
Memory Cd8 T Cells ◽  
Tumor Tissues ◽  
And Control

PurposeResident memory CD8 T cells, owing to their ability to reside and persist in peripheral tissues, impart adaptive sentinel activity and amplify local immune response, and have beneficial implications for tumor surveillance and control. The current study aimed to clarify the less known chemotactic mechanisms that govern the localization, retention, and residency of memory CD8 T cells in the ovarian tumor microenvironment.Experimental designRNA and protein expressions of chemokine receptors in CD8+ resident memory T cells in human ovarian tumor-infiltrating CD8+ T cells and their association with survival were analyzed. The role of CXCR6 on antitumor T cells was investigated using prophylactic vaccine models in murine ovarian cancer.ResultsChemokine receptor profiling of CD8+CD103+ resident memory tumor-infiltrating lymphocytes in patients with ovarian cancer revealed high expression of CXCR6. Analysis of The Cancer Genome Atlas (TCGA) (ovarian cancer database revealed CXCR6 to be associated with CD103 and increased patient survival. Functional studies in mouse models of ovarian cancer revealed that CXCR6 is a marker of resident, but not circulatory, tumor-specific memory CD8+ T cells. CXCR6-deficient tumor-specific CD8+ T cells showed reduced retention in tumor tissues, leading to diminished resident memory responses and poor control of ovarian cancer.ConclusionsCXCR6, by promoting retention in tumor tissues, serves a critical role in resident memory T cell-mediated immunosurveillance and control of ovarian cancer. Future studies warrant exploiting CXCR6 to promote resident memory responses in cancers.

scholarly journals TGF-[beta]-dependent Lymphoid Tissue Residency of Stem-like T cells Limits the Response to Tumor Vaccine

2021 ◽  
Author(s):  
Guo Li ◽  
Liwen Wang ◽  
Chaoyu Ma ◽  
Wei Liao ◽  
Yong Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Memory T Cells ◽  
Tumor Vaccine ◽  
Tumor Control ◽  
Lymphoid Tissues ◽  
Dependent Manner ◽  
Multiple Tumor ◽  
Draining Lymph Node ◽  
Resident Memory T Cells

Stem-like CD8+ T cells represent the key subset responding to multiple tumor immunotherapies, including tumor vaccination. However, the signals that control the differentiation of stem-like T cells are not entirely known. Most previous investigations on stem-like T cells are focused on tumor infiltrating T cells (TIL). The behavior of stem-like T cells in other tissues remains to be elucidated. Tissue-resident memory T cells (TRM) are often defined as a non-circulating T cell population residing in non-lymphoid tissues. TILs carrying TRM features are associated with better tumor control. Here, we found that stem-like CD8+ T cells differentiated into TRMs in a TGF-β and tumor antigen dependent manner almost exclusively in tumor draining lymph node (TDLN). TDLN-resident stem-like T cells were negatively associated with the response to tumor vaccine. In other words, after tumor vaccine, TDLN stem-like T cells transiently lost TRM features, differentiated into migratory effectors and exerted tumor control.

Should I stay or should I go—Reconciling clashing perspectives on CD4+ tissue-resident memory T cells

2019 ◽  
Vol 4 (37) ◽  
pp. eaax5595 ◽  
Author(s):  
Francis R. Carbone ◽  
Thomas Gebhardt
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Memory Cell ◽  
Cell Retention ◽  
Resident Memory T Cells

Two recent studies on CD4+ T cells in nonlymphoid tissues reveal a combination of memory cell retention and emigration.

Ovarian Cancer Immunogenicity is Governed by a Narrow Subset of Progenitor Tissue-Resident Memory T-Cells

2021 ◽  
Author(s):  
Carmen M. Anadon ◽  
Xiaoqing Yu ◽  
Subir Biswas ◽  
Ricardo A. Chaurio ◽  
Kay Hanggi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Memory T Cells ◽  
Resident Memory T Cells

scholarly journals Erratum: Programs for the persistence, vigilance and control of human CD8+ lung-resident memory T cells

2017 ◽  
Vol 18 (2) ◽  
pp. 246-246 ◽  
Author(s):  
Pleun Hombrink ◽  
Christina Helbig ◽  
Ronald A Backer ◽  
Berber Piet ◽  
Anna E Oja ◽  
...  
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Resident Memory T Cells ◽  
And Control

Programs for the persistence, vigilance and control of human CD8+ lung-resident memory T cells

2016 ◽  
Vol 17 (12) ◽  
pp. 1467-1478 ◽  
Author(s):  
Pleun Hombrink ◽  
Christina Helbig ◽  
Ronald A Backer ◽  
Berber Piet ◽  
Anna E Oja ◽  
...  
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Resident Memory T Cells ◽  
And Control

scholarly journals The Emerging Interplay Between Recirculating and Tissue-Resident Memory T Cells in Cancer Immunity: Lessons Learned From PD-1/PD-L1 Blockade Therapy and Remaining Gaps

2021 ◽  
Vol 12 ◽  
Author(s):  
Silvia Gitto ◽  
Ambra Natalini ◽  
Fabrizio Antonangeli ◽  
Francesca Di Rosa
Keyword(s):  
T Cells ◽  
T Cell ◽  
Solid Tumors ◽  
Memory T Cells ◽  
Tumor Therapy ◽  
T Cell Response ◽  
Lessons Learned ◽  
Tumor Control ◽  
Specific Memory ◽  
Resident Memory T Cells

Remarkable progress has been made in the field of anti-tumor immunity, nevertheless many questions are still open. Thus, even though memory T cells have been implicated in long-term anti-tumor protection, particularly in prevention of cancer recurrence, the bases of their variable effectiveness in tumor patients are poorly understood. Two types of memory T cells have been described according to their traffic pathways: recirculating and tissue-resident memory T cells. Recirculating tumor-specific memory T cells are found in the cell infiltrate of solid tumors, in the lymph and in the peripheral blood, and they constantly migrate in and out of lymph nodes, spleen, and bone marrow. Tissue-resident tumor-specific memory T cells (TRM) permanently reside in the tumor, providing local protection.Anti-PD-1/PD-L1, a type of immune checkpoint blockade (ICB) therapy, can considerably re-invigorate T cell response and lead to successful tumor control, even in patients at advanced stages. Indeed, ICB has led to unprecedented successes against many types of cancers, starting a ground-breaking revolution in tumor therapy. Unfortunately, not all patients are responsive to such treatment, thus further improvements are urgently needed. The mechanisms underlying resistance to ICB are still largely unknown. A better knowledge of the dynamics of the immune response driven by the two types of memory T cells before and after anti-PD-1/PD-L1 would provide important insights on the variability of the outcomes. This would be instrumental to design new treatments to overcome resistance.Here we provide an overview of T cell contribution to immunity against solid tumors, focusing on memory T cells. We summarize recent evidence on the involvement of recirculating memory T cells and TRM in anti-PD-1/PD-L1-elicited antitumor immunity, outline the open questions in the field, and propose that a synergic action of the two types of memory T cells is required to achieve a full response. We argue that a T-centric vision focused on the specific roles and the possible interplay between TRM and recirculating memory T cells will lead to a better understanding of anti-PD-1/PD-L1 mechanism of action, and provide new tools for improving ICB therapeutic strategy.

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