Pathology Services in Nigeria: Cross-Sectional Survey Results From Three Cancer Consortia.

PURPOSE: Cancer incidence is increasing in sub-Saharan Africa, yet there is little information on the capacity of pathology laboratories in this region. We aimed to assess the current state of pathology services in Nigeria to guide strategies to ensure best practices and improve the quality of surgical specimen handling. METHODS: We developed structured pathology survey to assess tissue handling, sample processing, and immunohistochemistry (IHC) capabilities. The survey was distributed electronically to 22 medical centers in Nigeria that are part of established cancer consortia. Data were collected between September and October 2017. RESULTS: Sixteen of 22 centers completed the survey in full. All 16 institutions had at least one board-certified pathologist and at least one full-time laboratory scientist/technologist. The majority of responding institutions (75%) reported processing fewer than 3,000 samples per year. For sample processing, 38% of institutions reported manual tissue processing and 75% processed biopsies and surgical specimens together. The average tissue fixation time ranged from 5 to more than 72 hours before processing and paraffin embedding. Half of the institutions reported having no quality assurance processes to evaluate hematoxylin and eosin-stained slides, and 25% reported having no written operating procedures. Half of the participating institutions have a facility for routine IHC staining, and among these there was considerable variability in processes and validation procedures. External proficiency testing was not common among surveyed sites (38%). CONCLUSION: Data from 16 Nigerian medical institutions indicate deficiencies in standardization, quality control, and IHC validation that could affect the reliability of pathology results. These findings highlight addressable gaps in pathology services that can ensure accurate diagnosis and follow-up for the growing number of patients with cancer in this region.

Myeloid-derived suppressor cells and anti-tumor T cells: a complex relationship.

Myeloid-Derived Suppressor Cells (MDSC) are immature myeloid cells that are potent inhibitors of immune cell function and which accumulate under conditions of inflammation, especially cancer. MDSC are suggested to promote the growth of cancer by both enhancement of tumor angiogenesis and metastasis and also inhibition of antitumor immune responses. The presence of deficient and/or defective antitumor adaptive and innate immune responses, coincident with accumulation of MDSC in lymphoid organs and tumor parenchyma, supports the notion of a causal relationship. The potent ability of MDSC to inhibit several components and phases of immune response highlights the likelihood that targeting the inhibitory functions of MDSC may maximize the therapeutic potential of antitumor immunotherapy. In order to guide the rational development of immunotherapeutic strategies that incorporate inhibition of MDSC activity and enzymatic functions, thorough understanding of the role of MDSC in antitumor immune responses is required. In this manuscript we review the multifaceted inhibitory functions of MDSC and consider the role of MDSC-induced inhibition of antitumor T cell effector phase. Support for this research is from NIH R01 CA108573.

Protocadherin-18 is a novel differentiation marker and an inhibitory signaling receptor for CD8+ effector memory T cells.

CD8(+) tumor infiltrating T cells (TIL) lack effector-phase functions due to defective proximal TCR-mediated signaling previously shown to result from inactivation of p56(lck) kinase. We identify a novel interacting partner for p56(lck) in nonlytic TIL, Protocadherin-18 ('pcdh18'), and show that pcdh18 is transcribed upon in vitro or in vivo activation of all CD8(+) central memory T cells (CD44(+)CD62L(hi)CD127(+)) coincident with conversion into effector memory cells (CD44(+)CD62L(lo)CD127(+)). Expression of pcdh18 in primary CD8(+) effector cells induces the phenotype of nonlytic TIL: defective proximal TCR signaling, cytokine secretion, and cytolysis, and enhanced AICD. pcdh18 contains a motif (centered at Y842) shared with src kinases (QGQYQP) that is required for the inhibitory phenotype. Thus, pcdh18 is a novel activation marker of CD8(+) memory T cells that can function as an inhibitory signaling receptor and restrict the effector phase.

Tumor-induced disruption of proximal TCR-mediated signal transduction in tumor-infiltrating CD8+ lymphocytes inactivates antitumor effector phase.

The presence in cancer tissue of Ag-specific, activated tumor infiltrating CD8(+) T cells proves that tumors express Ags capable of eliciting immune response. Therefore, in general, tumor escape from immune-mediated clearance is not attributable to immunological ignorance. However, tumor-infiltrating lymphocytes are defective in effector phase function, demonstrating tumor-induced immune suppression that likely underlies tumor escape. Since exocytosis of lytic granules is dependent upon TCR-mediated signal transduction, it is a reasonable contention that tumors may induce defective signal transduction in tumor infiltrating T cells. In this review, we consider the biochemical basis for antitumor T cell dysfunction, focusing on the role of inhibitory signaling receptors in restricting TCR-mediated signaling in tumor-infiltrating lymphocytes.