Immune checkpoint inhibitor treatment of a first cancer is associated with a decreased incidence of second primary cancer.

BACKGROUND: Second primary cancers (SPCs) are diagnosed in over 5% of patients after a first primary cancer (FPC). We explore here the impact of immune checkpoint inhibitors (ICIs) given for an FPC on the risk of SPC in different age groups, cancer types and treatments. PATIENTS AND METHODS: The files of the 46 829 patients diagnosed with an FPC in the Centre Léon Bérard from 2013 to 2018 were analyzed. Structured data were extracted and electronic patient records were screened using a natural language processing tool, with validation using manual screening of 2818 files of patients. Univariate and multivariate analyses of the incidence of SPC according to patient characteristics and treatment were conducted. RESULTS: Among the 46 829 patients, 1830 (3.9%) had a diagnosis of SPC with a median interval of 11.1 months (range 0-78 months); 18 128 (38.7%) received cytotoxic chemotherapy (CC) and 1163 (2.5%) received ICIs for the treatment of the FPC in this period. SPCs were observed in 7/1163 (0.6%) patients who had received ICIs for their FPC versus 437/16 997 (2.6%) patients receiving CC and no ICIs for the FPC versus 1386/28 669 (4.8%) for patients receiving neither CC nor ICIs for the FPC. This reduction was observed at all ages and for all histotypes analyzed. Treatment with ICIs and/or CC for the FPC are associated with a reduced risk of SPC in multivariate analysis. CONCLUSION: Immunotherapy with ICIs alone and in combination with CC was found to be associated with a reduced incidence of SPC for all ages and cancer types.

Low expression of ANT1 confers oncogenic properties to rhabdomyosarcoma tumor cells by modulating metabolism and death pathways.

Rhabdomyosarcoma (RMS) is the most frequent form of pediatric soft-tissue sarcoma. It is divided into two main subtypes: ERMS (embryonal) and ARMS (alveolar). Current treatments are based on chemotherapy, surgery, and radiotherapy. The 5-year survival rate has plateaued at 70% since 2000, despite several clinical trials. RMS cells are thought to derive from the muscle lineage. During development, myogenesis includes the expansion of muscle precursors, the elimination of those in excess by cell death and the differentiation of the remaining ones into myofibers. The notion that these processes may be hijacked by tumor cells to sustain their oncogenic transformation has emerged, with RMS being considered as the dark side of myogenesis. Thus, dissecting myogenic developmental programs could improve our understanding of RMS molecular etiology. We focused herein on ANT1, which is involved in myogenesis and is responsible for genetic disorders associated with muscle degeneration. ANT1 is a mitochondrial protein, which has a dual functionality, as it is involved both in metabolism via the regulation of ATP/ADP release from mitochondria and in regulated cell death as part of the mitochondrial permeability transition pore. Bioinformatics analyses of transcriptomic datasets revealed that ANT1 is expressed at low levels in RMS. Using the CRISPR-Cas9 technology, we showed that reduced ANT1 expression confers selective advantages to RMS cells in terms of proliferation and resistance to stress-induced death. These effects arise notably from an abnormal metabolic switch induced by ANT1 downregulation. Restoration of ANT1 expression using a Tet-On system is sufficient to prime tumor cells to death and to increase their sensitivity to chemotherapy. Based on our results, modulation of ANT1 expression and/or activity appears as an appealing therapeutic approach in RMS management.

Polymerase chain reaction amplified HTLV-I, HIV-1 and HIV-2 DNA fragments in subjects with mixed retroviral infections.

Serum and peripheral blood mononuclear cells from eight patients from the Ivory Coast with positive screening test results for retroviral infections were studied by serology (ELISA, Western blot (WB), synthetic peptide test), cell co-culture, and polymerase chain reaction (PCR). Two HIV-2 infections with indeterminate interpretation on HIV-1 WB were detected, two were clear dual HIV-1/HIV-2 infections, three were ambiguous mixed HIV-1/HIV-2 infections, and one was a triple retroviral infection by HTLV-I, HIV-1 and HIV-2. Four slow/low HIV-1 strains were isolated at the expense of HTLV-I and HIV-2 strains. The ELISA tests were found to be very sensitive. Indeterminate WB interpretations were frequent (HTLV-I, four; HIV-1, three; HIV-2, two). PCR provided clear evidence of multiple retroviral infections in three cases and enabled interpretation of indeterminate WB samples in three cases. One sample presented a puzzling pattern with positive PCR results for HIV-1 and HIV-2 associated with negative or indeterminate serological results. Thus, our data emphasise the need to analyse serological as well as virological markers to gain better insight on mixed retroviral infections, especially in endemic areas such as West Africa.

[Anti-BCG antibody titers in healthy and leprous Africans. Value of an indirect immunoperoxidase test]. / Titrage d'anticorps anti-BCG chez des Africains sains et lépreux. Intérêt d'un test indirect à l'immuno-peroxydase.

An immunoperoxidase reaction was used for the titration of immunoglobulins G and M antibodies to BCG in 171 leprosy patients from Dakar. The results show mean titers decreasing from lepromatous to tuberculoid cases. The antibody profiles of some clinical forms such as reverse reactions, erythema nodosum leprosum are discussed. This test associated to the Mitsuda reaction, bacteriology and histology should allow an easier classification of the borderline forms. The main advantages of the technique are simplicity, speed, low cost and the easy availability of the BCG. These qualities are essential in endemic zone.

[Anti-BCG titers of healthy and tuberculous Africans. Use of the indirect immunoperoxidase test]. / Titrage d'anticorps anti-BCG chez des africains sains et tuberculeux. Utilisation d'un test indirect à l'immuno-peroxydase.

This study was intended to assess the presence of antibodies to BCG: immunoglobulin G (IgG) and immunoglobulin M (IgM) in three homogenous african populations: 76 tuberculous patients, 55 adult healthy subjects and 46 newborn. We have used an indirect immuno-peroxidase reaction. Tuberculous patients were clearly distinguished from the other two groups by raised IgG titres, associated with severe clinical and radiological features. In the control population, the IgG anti-BCG were also present, but to a lesser degree. The IgM anti-BCG were seen in high titres (greater than 20 in this study) in healthy adults and patients. The two populations differed significantly (p less than 0.001), nevertheless some healthy adults achieved IgM titres comparable with tuberculous patients. This simple test could be an interesting contributory factor in cases of diagnostic difficult and enables a serological assessment of patients having BCG therapy.