Isolation and In vitro expansion of lymphocytes infiltrating non-small cell lung carcinoma: Functional and molecular characterisation for their use in adoptive immunotherapy

Melioli, Giovanni; Meta, Maurizio; Semino, Claudia; Casartelli, Gianluigi; Pasquetti, W; Biassoni, Roberto; Ratto, G. B.; Catrullo, A.; Moretta, Lorenzo; Guastella, Marina

doi:10.1016/s0959-8049(05)80027-9

Cited by 35 publications

(12 citation statements)

References 13 publications

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“…On both samples a confirmatory histological analysis was retrospectively performed. Part of each sample was frozen for Western blot and for RT‐PCR analyses, and part was processed for cell separation, as previously described 19. Briefly, tissues were dissociated by sterile mechanical dissection and enzymatic digestion.…”

Section: Methodsmentioning

confidence: 99%

Arginase 2 is expressed by human lung cancer, but it neither induces immune suppression, nor affects disease progression

Rotondo¹,

Mastracci

Piazza³

et al. 2008

Intl Journal of Cancer

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In human prostate cancer, Arginase 2 (ARG2) and nitric oxide synthase (NOS) are concomitantly expressed by tumor cells, and induce tumor immune escape via peroxynitrite-dependent Tyrosine nitrosylation. Since there were no data regarding this immune suppressive mechanism in other tumor types, and an evaluation of its clinical relevance in human tumors had still to be provided, we have investigated presence and clinical relevance of ARG2 and NOS expression in lung cancer. No evidence of NOS expression was found, no significant NOS enzymatic activity was detected. Instead, ARG2 protein was expressed by tumor cells. In a cohort of 120 patients, the amount of ARG2-positive tumor cells was significantly higher in small cell lung cancers (SCLC) than in nonsmall cell lung cancers (NSCLC). Large cell undifferentiated carcinomas had twice ARG2 than the other NSCLC subtypes. ARG2 expression was increased in Grade 3 tumors, as compared to Grades 1 and 2. However, no relationship was found with tumor size and stage, and with patient survival. Indeed, the enzyme was active, since the Arginine catabolite Ornithine was produced, but Arginine depletion was not attained. In addition, nitrotyrosine was not found in tumor tissue. Accordingly, when tumor cells isolated from lung cancer were incubated with activated autologous T cells, no inhibition of proliferation was detected. Our results indicate that ARG2 is expressed in lung cancer, but it does not induce tumor immune escape and does not affect disease progression, most probably due to the lack of concomitant NOS expression.

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Section: Methodsmentioning

confidence: 99%

Arginase 2 is expressed by human lung cancer, but it neither induces immune suppression, nor affects disease progression

Rotondo¹,

Mastracci

Piazza³

et al. 2008

Intl Journal of Cancer

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“…In lung cancer, oligoclonal T-cell populations isolated either from TIL or draining lymph nodes of advanced NSCLC can be expanded in vitro in the presence of IL-2, and have the ability to lyse autologous cancer cells [112][113][114]. Some, MHC class I-restricted CTL lines or clones that show specificity for autologous NSCLC cells or SCLC cells have been obtained from peripheral blood lymphocytes.…”

Section: Specific Cytotoxic T-lymphocytes (Ctl)mentioning

confidence: 99%

Pulmonary perspective: immunology in diagnosis and treatment of lung cancer

Weynants

Marchandise²,

Sibille³

1997

Eur Respir J

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“…Tumor-reactive T cells were already detected in the mid 1990s in NSCLC lesions (16)(17)(18), and a clinical effect of TIL therapy for stage IV NSCLC patients has been reported, albeit with very minor improvements in survival (19). Since that time, the treatment regimen substantially improved, by speeding up the protocols to culture and expand TILs from tumor lesions (1,2), and by pre-conditioning the patient with nonmyeloablative chemotherapy (20) that allowed for the above-mentioned success rates in melanoma patients.…”

Section: Introductionmentioning

confidence: 99%

Polyfunctional tumor-reactive T cells are effectively expanded from non-small cell lung cancers, and correlate with an immune-engaged T cell profile

Groot

Loenen

Guislain

et al. 2018

Preprint

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Non-small cell lung cancer (NSCLC) is the second most prevalent type of cancer.With the current treatment regimens, the mortality rate remains high. Therefore, better therapeutic approaches are necessary. NSCLCs generally possess many genetic mutations and are well infiltrated by T cells (TIL), making TIL therapy an attractive option. Here we show that T cells from treatment naive, stage I-IVa NSCLC tumors can effectively be isolated and expanded, with similar efficiency as from normal lung tissue. Importantly, 76% (13/17) of tested TIL products isolates from NSCLC lesions exhibited clear reactivity against primary tumor digests, with 0.5%-30% of T cells producing the inflammatory cytokine Interferon (IFN)-γ. Both CD4 + and CD8 + T cells displayed tumor reactivity. The cytokine production correlated well with CD137 and CD40L expression. Furthermore, almost half (7/17) of the TIL products contained polyfunctional T cells that produced Tumor Necrosis Factor (TNF)-α and/or IL-2 in addition to IFN-γ, a hallmark of effective immune responses. Tumor-reactivity in the TIL products correlated with high percentages of CD103 + CD69 + CD8 + T cell infiltrates in the tumor lesions, with PD-1 hi CD4 + T cells, and with FoxP3 + CD25 + CD4 + regulatory T cell infiltrates, suggesting that the composition of T cell infiltrates may predict the level of tumor reactivity. In conclusion, the effective generation of tumor-reactive and polyfunctional TIL products implies that TIL therapy will be a successful treatment regimen for NSCLC patients.

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Isolation and In vitro expansion of lymphocytes infiltrating non-small cell lung carcinoma: Functional and molecular characterisation for their use in adoptive immunotherapy

Cited by 35 publications

References 13 publications

Arginase 2 is expressed by human lung cancer, but it neither induces immune suppression, nor affects disease progression

Arginase 2 is expressed by human lung cancer, but it neither induces immune suppression, nor affects disease progression

Pulmonary perspective: immunology in diagnosis and treatment of lung cancer

Polyfunctional tumor-reactive T cells are effectively expanded from non-small cell lung cancers, and correlate with an immune-engaged T cell profile

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