Intratumoral T Cells, Recurrence, and Survival in Epithelial Ovarian Cancer

Zhang, Lin; Conejo-Garcia, José R.; Katsaros, Dionyssios; Gimotty, Phyllis A.; Massobrio, M; Regnani, Giorgia; Makrigiannakis, Antonis; Gray, Heidi J.; Schlienger, Katia; Liebman, Michael; Rubin, Stephen C.; Coukos, George

doi:10.1056/nejmoa020177

Cited by 3,031 publications

(2,480 citation statements)

References 33 publications

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“…Even with immune recognition of cancer, which can occur in cancer patients and is evidenced by the frequent observation of T cell infiltration into cancerous tissues [70][71][72][73], it is rare for such tumor infiltrating T cells to induce the spontaneous rejection of established tumors. Accumulating evidence indicates that the tumor environment contains cells and cytokines that actively suppress primed effector T cells [74,75].…”

Section: The Immunosuppressive Environment Inside Tumorsmentioning

confidence: 99%

Targeting tumors with LIGHT to generate metastasis-clearing immunity

Yü¹,

Fu²

2008

Cytokine & Growth Factor Reviews

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Metastastic diseases cause the majority of morbidity and mortality of cancer patients. Established tumors form both physical and immunological barriers to limit immune detection and destruction. Current immunotherapy of vaccination and adoptive transfer shows limited effect at least in part due to the existing barriers in the tumors and depending on the knowledge of tumor antigens. Tumor necrosis factor superfamily member 14 (TNFSF14) LIGHT interacts with stromal cells, dendritic cells, NK cells, naïve and activated T cells and tumor cells inside the tumor tissues via its two functional receptors, HVEM and lymphotoxin β receptor (LTβR). Targeting tumor tissues with LIGHT leads to augmentation of priming, recruitment, and retention of effector cells at tumor sites, directly or indirectly, to induce strong anti-tumor immunity to inhibit the growth of primary tumors as well as eradicate metastases. Intratumor treatment would break tumor barriers and allow strong immunity against various tumors without defining tumor antigens. This review summarizes recent findings to support that LIGHT is a promising candidate for an effective cancer immunotherapy.

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Section: The Immunosuppressive Environment Inside Tumorsmentioning

confidence: 99%

Targeting tumors with LIGHT to generate metastasis-clearing immunity

Yü¹,

Fu²

2008

Cytokine & Growth Factor Reviews

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show abstract

“…To this end, presence of tumor infiltrating lymphocytes (TILs) has been shown to correlate with better prognosis of several solid cancers including MM, 7 colon carcinoma, 8 ovarian cancer 9 and breast cancer. 10 This is supported by accumulating data linking response to immune therapy with a brisk infiltration of T cells in the tumor.…”

Section: Introductionmentioning

confidence: 99%

Chemokine receptor engineering of T cells with CXCR2 improves homing towards subcutaneous human melanomas in xenograft mouse model

et al. 2018

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Adoptive cell therapy (ACT) using in vitro expanded tumor infiltrating T lymphocytes (TILs) from biopsy material represents a highly promising treatment of disseminated cancer. A crucial prerequisite for successful ACT is sufficient recruitment of transferred lymphocytes to the tumor site; however, despite infusion of billions of lymphocytes, T cell infiltration into the tumor post ACT is limited. By PCR and Luminex analyses we found that a majority of malignant melanoma (MM) cell lines expressed chemokines CXCL1/Groα, CXCL8/IL-8, CXCL12/SDF-1 and CCL2. Concerning expression of the corresponding receptors on T cells, only the IL-8 receptor, CXCR2, was not expressed on T cells. CXCR2 was therefore expressed in T cells by lentiviral transduction, and shown to lead to ligand specific transwell migration of engineered T cells, as well as increased migration towards MM conditioned medium. In vivo homing was assessed in a xenograft NOG mouse model. Mice with subcutaneous human melanoma were treated with MAGE-A3 specific T cells transduced with either CXCR2 or MOCK. Transducing T cells carrying the MAGE-A3a3a high affinity T cell receptor with CXCR2 increased tumor infiltration. Flow cytometry analysis 7 days after ACT showed a doubling in CD3+ T cells in tumor digest of mice receiving CXCR2 transduced T cells compared to MOCK treated mice, a finding confirmed by immunohistochemistry. In conclusion, our CXCR2 transduced T cells are functional in vitro and transduction with CXCR2 increases in vivo homing of T cells to tumor site.

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“…The presence of tumor‐infiltrating T cells correlates with a favorable clinical outcome for cancer,22, 23 and adoptive immunotherapy, such as cytokine‐induced killer (CIK) cells, has shown objective clinical responses in many solid tumors 24, 25. Furthermore, improved clinical activity was observed in cancer patients treated with a combination of epigenetic therapy and adoptive immunotherapy,12, 26 and HMA may play an immune stimulatory role in cancer therapy by sensitizing patients to immune responses 21, 27.…”

Section: Introductionmentioning

confidence: 99%

Phase Ib/II study of safety and efficacy of low‐dose decitabine‐primed chemoimmunotherapy in patients with drug‐resistant relapsed/refractory alimentary tract cancer

Chen

Nie

Liu

et al. 2018

Intl Journal of Cancer

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The pressing need for improved therapeutic outcomes provides a good rationale for identifying effective strategies for alimentary tract (AT) cancer treatment. The potential re‐sensitivity property to chemo‐ and immunotherapy of low‐dose decitabine has been evident both preclinically and in previous phase I trials. We conducted a phase Ib/II trial evaluating low‐dose decitabine‐primed chemoimmunotherapy in patients with drug‐resistant relapsed/refractory (R/R) esophageal, gastric or colorectal cancers. Forty‐five patients received either the 5‐day decitabine treatment with subsequent readministration of the previously resistant chemotherapy (decitabine‐primed chemotherapy, D‐C cohort) or the aforementioned regimen followed by cytokine‐induced killer cells therapy (D‐C and cytokine‐induced killer [CIK] cell treatment, D‐C + CIK cohort) based on their treatment history. Grade 3 to 4 adverse events (AEs) were reported in 11 (24.4%) of 45 patients. All AEs were controllable, and no patient experienced a treatment‐related death. The objective response rate (ORR) and disease control rate (DCR) were 24.44% and 82.22%, respectively, including two patients who achieved durable complete responses. Clinical response could be associated with treatment‐free interval and initial surgical resection history. ORR and DCR reached 28% and 92%, respectively, in the D‐C + CIK cohort. Consistently, the progression‐free survival (PFS) of the D‐C + CIK cohort compared favorably to the best PFS of the pre‐resistant unprimed therapy (p = 0.0001). The toxicity and ORRs exhibited were non‐significantly different between cancer types and treatment cohort. The safety and efficacy of decitabine‐primed re‐sensitization to chemoimmunotherapy is attractive and promising. These data warrant further large‐scale evaluation of drug‐resistant R/R AT cancer patients with advanced stage disease.

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Intratumoral T Cells, Recurrence, and Survival in Epithelial Ovarian Cancer

Abstract: The presence of intratumoral T cells correlates with improved clinical outcome in advanced ovarian carcinoma.

Cited by 3,031 publications

References 33 publications

Targeting tumors with LIGHT to generate metastasis-clearing immunity

Targeting tumors with LIGHT to generate metastasis-clearing immunity

Chemokine receptor engineering of T cells with CXCR2 improves homing towards subcutaneous human melanomas in xenograft mouse model

Phase Ib/II study of safety and efficacy of low‐dose decitabine‐primed chemoimmunotherapy in patients with drug‐resistant relapsed/refractory alimentary tract cancer

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