ex-vivo-imaging-resident-cd8-t-lymphocytes-human-lung-tumor-slices

<em>Ex Vivo</em> Imaging of Resident CD8 T Lymphocytes in Human Lung Tumor Slices Using Confocal Microscopy

CD8 T cell are key players in the fight against cancer. In order for CD8 T cells to kill tumor cells they need to enter into the tumor, migrate within the ...

University Paris Descartes

Tumor-infiltrating T cells, particularly CD45RO(+)CD8(+) memory T cells, confer a positive prognostic value in human cancers. However, the mechanisms that promote a protective T-cell response in the tumor microenvironment remain unclear. In chronic inflammatory settings such as the tumor microenvironment, lymphoid neogenesis can occur to create local lymph node-like structures known as tertiary lymphoid structures (TLS). These structures can exacerbate a local immune response, such that TLS formation in tumors may help promote an efficacious immune contexture. However, the role of TLS in tumors has yet to be investigated carefully. In lung tumors, mature dendritic cells (DC) present in tumor-associated TLS can provide a specific marker of these structures. In this study, we evaluated the influence of TLS on the characteristics of the immune infiltrate in cohorts of prospective and retrospective human primary lung tumors (n = 458). We found that a high density of mature DC correlated closely to a strong infiltration of T cells that are predominantly of the effector-memory phenotype. Moreover, mature DC density correlated with expression of genes related to T-cell activation, T-helper 1 (Th1) phenotype, and cytotoxic orientation. Lastly, a high density of TLS-associated DC correlated with long-term survival, which also allowed a distinction of patients with high CD8(+) T-cell infiltration but a high risk of death. Taken together, our results show how tumors infiltrated by TLS-associated mature DC generate a specific immune contexture characterized by a strong Th1 and cytotoxic orientation that confers the lowest risk of death. Furthermore, our findings highlight the pivotal function of TLS in shaping the immune character of the tumor microenvironment, in promoting a protective immune response mediated by T cells against cancer.

Dendritic cells in tumor-associated tertiary lymphoid structures signal a Th1 cytotoxic immune contexture and license the positive prognostic value of infiltrating CD8+ T cells.

Hypothesizing that nutritional status, systemic inflammation and tumoral immune microenvironment play a role as determinants of lung cancer evolution, the purpose of this study was to assess their respective impact on long-term survival in resected non-small cell lung cancers (NSCLC).

Systemic inflammation, nutritional status and tumor immune microenvironment determine outcome of resected non-small cell lung cancer.

Surgery is still the best treatment option of lung cancer but only one third of patients are operable and prognosis remains mediocre in operated patients, with the exception of initial stages. Medical treatment is fast moving toward new frontiers. New insights in the biology of cancer development led to discovery of new drugs, which are more effective as compared to conventional platinum based chemotherapy. A new approach to immunotherapy based on immune-check point represents a remarkable innovation in lung cancer treatment. Initial trials with anti PD-1 antibodies in metastatic patients provided results never observed with previously known drug categories. Several key question need to be answered to identify patients most likely to respond to anti PD-1/anti PD-L1 treatments, to assess the role of combined treatment modalities including immune check point receptor block (associations with surgery, chemotherapy, ITKs), and to boost host immune response, possibly by lowering his systemic inflammation and improving nutritional status.

Immune therapy of non-small cell lung cancer. The future.

Hypothesizing that morphometric measurements are reliable markers of fitness in patients with lung cancer requiring aggressive surgical intervention, the purpose of this study was to assess their impact on postoperative outcome and long-term survival in patients with non-small cell lung cancer (NSCLC) requiring pneumonectomy.

Body Mass Index and Total Psoas Area Affect Outcomes in Patients Undergoing Pneumonectomy for Cancer.

Histological subdivision into typical (TC) and atypical (AC) is crucial for treatment and prognosis of lung carcinoids but can be also very challenging, even for experts. In this study, we aimed to strengthen or reduce the prognostic value of several pathological, clinical, or per-operative factors some of which are still controversial.

Article	Year
Dendritic cells in tumor-associated tertiary lymphoid structures signal a Th1 cytotoxic immune contexture and license the positive prognostic value of infiltrating CD8+ T cells. Cancer research\| PubMed ID: 24366885	2014
Systemic inflammation, nutritional status and tumor immune microenvironment determine outcome of resected non-small cell lung cancer. PloS one\| PubMed ID: 25238252	2014
Immune therapy of non-small cell lung cancer. The future. Pharmacological research\| PubMed ID: 26141705	2015
Body Mass Index and Total Psoas Area Affect Outcomes in Patients Undergoing Pneumonectomy for Cancer. The Annals of thoracic surgery\| PubMed ID: 27659598	2017
Surgical Resection for Pulmonary Carcinoid: Long-Term Results of Multicentric Study-The Importance of Pathological N Status, More Than We Thought. Lung\| PubMed ID: 29022070	2017

Marco Alifano

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