Neoadjuvant Gene-Mediated Cytotoxic Immunotherapy for Non-Small-Cell Lung Cancer: Safety and Immunologic Activity

Predina, Jarrod D.; Haas, Andrew R.; Martínez, Marina; O’Brien, Shaun; Moon, Edmund K.; Woodruff, Patrick; Stadanlick, Jason; Corbett, Christopher; Frenzel-Sulyok, Lydia G; Bryski, Mitchell G.; Eruslanov, Evgeniy; Deshpande, Charuhas; Langer, Corey J.; Aguilar, Laura K.; Guzik, Brian W.; Manzanera, Andrea G.; Aguilar-Córdova, Estuardo; Singhal, Sunil; Albelda, Steven Μ.

doi:10.1016/j.ymthe.2020.11.001

Cited by 9 publications

(8 citation statements)

References 44 publications

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“…We observed higher percentages of CD8+ HLA-DR+ T cells in peripheral blood from R patients, suggesting, in line with studies in other neoplasias, an increased activation of these cells [ 14 , 15 ]. We can speculate that this increased CD8+ T cell activation is the consequence of high proliferative tumors where NACT is more effective.…”

Section: Discussionsupporting

confidence: 90%

“…Furthermore, a specific increase in CD8+ T cells and a decrease in CD4+ T cells and B cells [ 11 , 12 ] in post-NACT residual breast tumors is associated with improved survival [ 13 ]. HLA-DR is a marker of T cell activation and was recently shown to be increased on CD8+ T cells of different cancer types [ 14 , 15 ]. These cells, which are mainly activated by antigens or cytokines, induce apoptosis in target cells via two main pathways: lytic (cytotoxicity) and non-lytic (cytokine production) mechanisms [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Effector Mechanisms of CD8+ HLA-DR+ T Cells in Breast Cancer Patients Who Respond to Neoadjuvant Chemotherapy

Osuna-Gómez

Arqueros

Galano

et al. 2021

Cancers

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Cytotoxic T lymphocyte (CTLs) activation is an independent predictor of response to neoadjuvant chemotherapy (NACT) in breast cancer (BC) patients. Here, we go deeper into the function of CD8+ HLA-DR+T cells from NACT treated HER2 negative BC patients. Flow cytometry analysis revealed that CD8+ HLA-DR+ T cell percentage was increased in NACT responder (R) compared to non-responder (NR) patients. R patients with ER-/PR- hormone receptors had the highest CD8+HLA-DR+T cell frequencies, while no differences were found when patients were classified according to cancer stage or menopause status. Interestingly, the cytotoxicity and production of anti-tumor cytokines were enhanced when CD8+ HLA-DR+ T cells from healthy donors were cultured with plasma from R, but not from NR patients. The induced anti-tumor profile of CD8+ HLA-DR+ T cells was associated with plasmatic IL-12 and IFN-γ levels, increased cytokines in R patients. IL-12 or IFN-γ neutralization decreased cytotoxic activity and TNF-α production by cultured CD8+ HLA-DR+ T cells in R plasma presence. All these data suggest that an effective response to NACT in BC patients is associated with increased IL-12 or IFN-γ levels involved in the induction of cytotoxic and pro-inflammatory mechanisms in CD8+ HLA-DR+ T cells.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Effector Mechanisms of CD8+ HLA-DR+ T Cells in Breast Cancer Patients Who Respond to Neoadjuvant Chemotherapy

Osuna-Gómez

Arqueros

Galano

et al. 2021

Cancers

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“…Likewise, it is similarly assumable that LA-NSCLC with a more advanced disease at presentation may be more frequently addressed to adjuvant therapy. Only focused randomized clinical trials may clarify the benefit of adjuvant therapy in this subset of patients, but hopefully, the advent of immunotherapy will completely revolutionize the overall treatment paradigm of resectable LA-NSCLC in a few years [25][26][27][28], as suggested by preliminary results [29,30].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Factors and Long-Term Survival in Locally Advanced NSCLC with Pathological Complete Response after Surgical Resection Following Neoadjuvant Therapy

Lococo

Sassorossi

Nachira

et al. 2020

Cancers

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Background: Outcomes for locally advanced NSCLC with pathological complete response (pCR), i.e., pT0N0 after induction chemoradiotherapy (IT), have been seldom investigated. Herein, long-term results, in this highly selected group of patients, have been evaluated with the aim to identify prognostic predictive factors. Methods: Patients affected by locally advanced NSCLC (cT1-T4/N0-2/M0) who underwent IT, possibly following surgery, from January 1992 to December 2019, were considered for this retrospective analysis. Survival rates and prognostic factors have been studied with Kaplan-Meier analysis, log-rank and Cox regression analysis. Results: Three-hundred and forty-three consecutive patients underwent IT in the considered period. Out of them, 279 were addressed to surgery; among them, pCR has been observed in 62 patients (18% of the total and 22% of the operated patients). In the pCR-group, clinical staging was IIb in 3 (5%) patients, IIIa in 28 (45%) patients and IIIb in 31 (50%). Surgery consisted of (bi)lobectomy in the majority of cases (80.7%), followed by pneumonectomy (19.3%). Adjuvant therapy was administered in 33 (53.2%) patients. Five-year overall survival and disease-free survival have been respectively 56.18% and 48.84%. The relative risk of death, observed with the Cox regression analysis, was 4.4 times higher (95% confidence interval (CI): 1.632–11.695, p = 0.03) for patients with N2 multi-station disease, 2.6 times higher (95% CI: 1.066–6.407, p = 0.036) for patients treated with pneumonectomy and 3 times higher (95% CI: 1.302–6.809, p = 0.01) for patients who did not receive adjuvant therapy. Conclusions: Rewarding long-term results could be expected in locally advanced NSCLC patients with pCR after IT followed by surgery. Baseline N2 single-station disease and adjuvant therapy after surgery seem to be associated with better prognosis, while pneumonectomy is associated with poorer outcomes.

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“…The GMCI method was found to be both safe and practicable. There was also a noticeable activation of the anti‐tumor immune response 81 …”

Section: Immunotherapeutic Agentsmentioning

confidence: 99%

“…There was also a noticeable activation of the antitumor immune response. 81 Dendritic cell (DC) based vaccines are also under investigation.…”

Section: Cancer Vaccinesmentioning

confidence: 99%

Effectiveness of immunological agents in non‐small cell lung cancer

et al. 2022

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Background and aim: Non-small cell lung cancer (NSCLC) continues to claim millions of lives worldwide. Although its poor prognosis is largely attributed to the lack of adequate and precise detection technologies, cancer cells' suppression of the immune system adds on to the difficulty of identifying abnormal NSCLC tumors in their early stages. Therefore, cancer immunotherapy, which activates the immune system and helps it fight tumors, has recently become the most sought-after technique, especially in the advanced stages of NSCLC, where surgery or chemotherapy may or may not bring about the desired survival benefits in patients.Methods: This review focuses on the various immunotherapeutic interventions and their efficacy in advanced NSCLC clinical trials. Monoclonal antibodies like anti-PD-1/PD-L1 agents and anti-CTLA-4 antibodies, cancer vaccines, oncolytic viruses and adoptive T cell therapy have been discussed in brief. Furthermore, the effects of gender, age, and race on the efficacy of immune checkpoint inhibitors and suggest plausible future approaches in the realm of immuno-oncology.Results: Immunotherapy is used alone or in combination either with other immunological agents or with chemotherapy. However, the efficacy of these strategies depends extensively on various demographic variables, as some patients respond perfectly well to immunotherapy, while others do not benefit at all or experience disease progression. By targeting a "hallmark" of cancer (immune evasion), immunotherapy has transformed NSCLC management, though several barriers prevent its complete effectiveness.Conclusions: All these immunological strategies should be interpreted in the current setting of synergistic treatment, in which these agents can be combined with chemotherapy, radiotherapy, and, or surgery following patient and tumor characteristics to proportionate the best-individualized treatment and achieve superior results. To better pursue this goal, further investigations on cost-effectiveness and sex-gender, race, and age differences in immunotherapy are needed.

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Neoadjuvant Gene-Mediated Cytotoxic Immunotherapy for Non-Small-Cell Lung Cancer: Safety and Immunologic Activity

Cited by 9 publications

References 44 publications

Effector Mechanisms of CD8+ HLA-DR+ T Cells in Breast Cancer Patients Who Respond to Neoadjuvant Chemotherapy

Effector Mechanisms of CD8+ HLA-DR+ T Cells in Breast Cancer Patients Who Respond to Neoadjuvant Chemotherapy

Prognostic Factors and Long-Term Survival in Locally Advanced NSCLC with Pathological Complete Response after Surgical Resection Following Neoadjuvant Therapy

Effectiveness of immunological agents in non‐small cell lung cancer

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