Which One Of These Is Characteristic Of Cancer Cells?

Cancer cell and cancerous tissue

Date of creation of the document 2011_2012


1, 1 Molecular cancer fundamentals 1. 1 Different environmental agents lead to the development of a cancer 1. 2 The three families of genes involved es in carcinogenesis â € ¢ 3 Control of expression and / or activation â € ¢ 1. 4 Activation factors â € ¢ 1. 5 Tumor progression and apoptosis 1. 6 Tumor progression and immortality: the cancer cell has unlimited proliferation

2 Functional and Morphological Changes â € ¢ 2. 1 Data Sheet of the Cancer Cell â € ¢ 2. 2 Changes to the Nucleus â € ¢ 2. 3 Changes in the Cytoplasm â € ¢ 2. 4 Membrane

Tumor Stroma 3. Quantitative Variations 3. 2 Qualitative Variations

4 Cancer and angiogenesis 4. 1 Vascularization in the periphery of tumors 4. 2 Vascularization in the center of tumors

Anti-tumor Immunity â € ¢ 1 Effectors of the anti-tumor immune response â € ¢ 2 Exhaust of tumors with the immune response â € ¢ 5. 3 Struggle Immunological Therapies


â € ¢ Describe the molecular basis of carcinogenesis and know a few examples in each of the three major families of genes (oncogenes, suppressor genes and genes of the genus). genetic homoeasis).

â € ¢ Know the great mechanisms of regulation of the expression or function of these genes.

â € ¢ Know the major genetic and environmental risk factors for cancer.

â € ¢ Find examples of cell cycle disruption and apoptosis in cancers.

â € ¢ Describe the biological and morphological characteristics of a cancer cell. Describe the cells that generally make up the tumor stroma.

â € ¢ Know the main features of tumor vascularization â € ¢ Know the big mechanisms of anti-tumor immune response.

Introduction The cancerous disease is characterized by the progressive invasion of the organ of origin, then of the whole organism, by cells become insensitive or insensitive to the mechanisms of homeopathy. Tissue and having acquired an ability of indefinite proliferation (immortalization).

These tumor cells in the vast majority of cases of a single cell (monoclonal). The peculiarities of tumor cells are related to the accumulation of alterations of their genome (genotype). These alterations are most often acquired during tumor genetics, but some may be of hereditary origin (family preferences).

Tumor clones may lose or maintain some morphological and functional characteristics of the original cells, or acquire new ones (variability of subclone phenotype).

These modifications will register both in the nucleus, in the cytoplasm and on the membrane of the pathological cells.


Neoplasma is the result of successive alterations of the tumor cell genome, which permanently disrupt tissue homeostasis (Figure 8.1).

Figure 8.1. Molecular basis of carcinogenesis

In the cancer cell, there is a permanent break in the equilibrium between intracellular signals: â € ¢ activation of stimulatory pathways; â € ¢ suppression of inhibitory pathways.

The coexistence of several events is necessary for the cancerous transformation. The activation of new oncogenes continues throughout the tumor progression: multi-step process.

1. 1 - Different agents of the environment lead to the development of cancer

â € ¢ Initiating agents: they induce a definite DNA release (eg mutation, breakage). Often, these carcinogens are activated by metabolic reactions.

Examples: â € ¢ chemical carcinogens: polycyclic aromatic hydrocarbons (petrol, tobacco),

aromatic amines (dyes, rubber industry), 2-naphthylamine, alkylating agents, aflatoxin b1;

â € ¢ virus (hepatitis B, Epstein-Barr, etc.); â € ¢ radiation. â € ¢ Promoting agents: they promote the expression of a genetic warrior, pre-eminently

induced by an initiator agent. They do not induce lesions of the DNA. The time elapsed between the initiation and the appearance of the tumors is reduced in the presence of promoters.

Examples: phorbol esters (TPA) (croton oil); â € ¢ hormones: Å "strogenae (breast cancer); â € ¢ nutrition: alcohol (ENT tumors), dietary fats (colonic cancers); â € ¢ schistosomiasis and bladder cancer.

1. 2 - The three families of genes involved in carcinogenesis Oncogenes

Some animal viruses are able to induce tumors (eg chicken rous sarcoma, discovered in 1911). The transforming properties of these viruses are due to the presence in their genome of particular sequences, viral oncogenes (v-onc).

These genes alone contain all the information for the transforming activity. These genes are altered forms of normal genes of cellular origin, the proto-oncogenes, captured by retroviruses during their replication.

Proto-oncogenes are conserved in all species (from insects to humans) and play an essential role in key steps of the control of the body. Embryogenesis or cell or tissue growth. These normal genes when they are reworked and / or over-expressed become oncogenes (c-onc). They can induce the appearance and / or development of a tumor.

Oncogenes are classically classified as: â € ¢ immortalizing genes (eg: c-myc) coding for nuclear proteins binding to

DNA; â € ¢ transforming genes (eg KRAS, RET, KIT) (Table 8.1)

Table 81: Examples of Proto-Oncogenes Involved in Human Tumors

Genes suppressors

Tumor suppressor genes (or anti-oncogenes) are inhibitors of cell growth. The inactivation of the product of these genes by loss of biallelic function results in the absence of a cell non-proliferation signal: it is a loss of function .

The first tumor suppressor gene described is the Rb gene of the reinoblastoma. The tumor suppressor gene most commonly implicated is TP53, with somatic mutations in many cancers and germline mutations in Li-Fraumeni syndrome.

Oncogenes and tumor suppressor genes encode proteins that are involved in major cellular functions: signaling, proliferation, differentiation, cycling, apoptosis (Table 8.2).

Table 82: Examples of tumor suppressor genes involved in human tumors

Integrity genes (care takers)

Pathogenic agents (X-rays, UV, hydrocarbons) can induce pinpoint lesions of the DNA (breakage of a strand, deletion, mutation of a base). Integrity-maintaining genes encode a multi-functional complex capable of monitoring the integrality of the genome (MSH2, MSH6.). In case of anomalies, different repair systems are put in place (BRCA1, rad50, MLH-1). If they fail, the lone cell dies by apoptosis.

The alteration of the 2 alleles of these genes leads to an increased susceptibility to cancer by genetic instability (accumulation of mutations leading to the activation of oncogenes or Inactivation of anti-oncogenes).

Mutations involving these three gene families are present in the majority of cancers. These lesions can be of environmental origin, under the effect of initiating agents, or on the contrary of genetic origin.

1. 3 - Control of the expression and / or activation of proto-oncogenes, tumor suppressor genes and genes for maintaining the integrity of the gà © nome.

Several mechanisms may be responsible for the expression and / or activation of the genes involved in tumorigenesis. These mechanisms are not mutually exclusive.

Point mutations, deletions, insertions (Figure 8.2)

For proto-oncogenes, a single genetic event is usually sufficient for (dominant) activation. For tumor suppressor genes and genome surveillance genes, a double event is necessary for the gene to be inactivated at the 2 allele levels (real). cessif).

Figure 8.2. Mutation of "function gain" of proto-oncogene KIT in a digestive stromal tumor

Sequencing after amplification of the DNA extracted from the tumor cells makes it possible to highlight a 6-base pair period. This deletion is responsible for the expression

of an oncogenic protein, because constitutively activated.

Genetic amplification

This phenomenon corresponds to a multiplication of the number of copies of a gene. This results in an increase in his expression. It is especially late in oncogenesis (Figure 8.3).

Figure 8.3. Detection of EGFR amplification by CISH (chromosome-revealed in situ hybridization) in colorectal adenocarcinoma

Chromosome adjustments

Translocations can lead to either the expression of a chimeric protein resulting from the fusion between two genes, or to the hyperexpression of an oncogene because of the transposition of the coding region of the latter in close proximity to regulating sequences of other genes.

Example 1: In chronic myeloid leukemia (CML) the reciprocal translocation between chromosomes 9 and 22 produces a shortened chromosome 22: the Philadelphia chromosome. This translocation results in a bcr / c-abl fusion gene encoding an activated tyrosine kinase. There is currently a therapeutic molecule capable of specifically blocking the tyrosine kinase activated by this translocation. Thanks to this therapy (Imatinib), the prognosis of CML has been transformed.

Example 2: In Burkitt's lymphoma, the translocation (8; 14) results in overexpression of the c-myc oncogene (chromosome 8) which is under the control of the heavy chain promoter immunoglobulins (chromosome 14).

Chromosomal deletions and complex chromosomal rearrangements

It can result in a loss of function of a tumor suppressor gene. This loss of function can be relational (ex: Rb) or dominant (ex: APC).

Epiphenetic mechanisms

The hypo- or hyper-methylation of genes or their regulatory sequences can modulate their transcription, whereas the sequence of DNA is normal. We speak of epigenetic mechanisms as opposed to genetic mechanisms, that is to say with alteration of the DNA.

1. 4 - Activating Factors Proto-oncogenes, tumor suppressor genes and genes to maintain the integrity of the genome.

Hedging factors

These genetic factors are responsible for family-related cancer preconceptions. Transmision can be dominant or reluctant, and the pendulum variable. Genetic predispositions to cancers are numerous, and monogenic prescriptions are best known (Table 8.3).

Table 8.3: Examples of familial tumor previsions in humans

Viral factors â € ¢ RNA trovirus. Some retroviruses are directly oncogenic, but it does not

There is a known example only in the animal. In humans, HTLV1 has been randomly integrated into the genome, it lacks oncogene but contains a transactivator gene (tax) capable of activate the genes of interleukin-2 and its receptor in T-lymphocytes.

â € ¢ Oncogenic DNA viruses: they do not contain an oncogenes type v-onc. Most often they seem to act by trans-activation of cellular genes (mutagenic insertional).

â € ¢ Other viruses act more indirectly. Example: The Epstein-Barr virus induces an intense polyclonal proliferation of infected B cells in immunodepressed subjects (HIV, endemic malaria, transplanted) and thus increases the risk of occurrence. chromosome translocations. During these somatic translocations, accidental juxtapositions of genes capable of activating proto-oncogenes may occur: the translocation t (8; 14): juxtaposition of c-myc and the gene of the constant region of immunoglobulins.

Physical Factors • Ionizing radiation promotes mutations and chromosomal breaks. â € ¢ Ultraviolet causes breaks in DNA, impossible to repair in people

patients with xeroderma pigmentosum (genetic anomaly); hence the occurrence of multiple skin cancers.

Chemical factors

There are many examples: â € ¢ tobacco; â € ¢ Aflatoxin induces very specific mutations of the P53 gene: carcinogen

hepatic; â € ¢ occupational cancers due to benzopyrene derivatives.

Tumor progression and cell cycle

The progression of the cell cycle is finely regulated by "points of control", which allow in particular a regulation of the speed of proliferation and a maintenance of the integrity of the cell. cellular genome. In many tumors, these control points are altered.

In case of cancer, extracellular or intracellular signals received by the cell will be able to activate the cyclin / cdk complexes or to alter the activity of the inhibitors (p21, p15, p16 ). The result will be the raising of the Rb lock and the entry of the cell in cycle.

Example: Cervical cancer of the uterus: Human papillomavirus (HPV) is a small double-stranded DNA virus that can infect epithelial tissues, most often asymptomatic. Certain high-risk HPV types (HPV 16, 18) are associated with cancer of the cervix of uterus. It is now known that this virus integrates into the genome of the host cell where it encodes viral proteins (e6 and e7) capable of binding and degrading p53 respectively. and Rb, which leads to a latch lifecycle of the cell cycle.

Learn more: Â "Recall on the normal cell cycle Â".

1. 5 - Tumor progression and apoptosis The cancer cell becomes resistant to apoptosis.

Apoptosis is implicated in the control of cellular homeostasis, and is under the control of many genes:

â € ¢ pro-apoptotic genes; example: P53, MYC (see diagram of the cell cycle); â € ¢ Survival or anti-apoptotic genes; example: BCL-2;

In case of DNA damage, the P53 gene is activated, allowing, through p21, the arrest of the cell cycle and the repair of the lesions. DNA or activation of apoptosis. There are abnormalities of the p53 gene in {23} cancers (mutations, deletions) leading to the suppression of the G1 checkpoint and therefore the apoptotic pathway in case of genetic instability or chromosomal abnormalities.

In follicular lymphoma, the t (14; 18) translocation results in the juxtaposition of the BCL-2 gene with the locus of the immunoglobulin heavy chain and leads to overexpression of the bcl-2 protein. The accumulation of this anti-apoptotic protein increases the survival of B lymphocytes, which increases the risk of acquiring new genetic abnormalities leading to the development of follicular lymphoma.

1. 6 - Tumor Progression and Immortality: The Cancer Cell Has Unlimited Proliferation Normal cells are programmed for a limited number of deletions (approximately 60â € "70 in vitro). At the ends of chromosomes are repetitive sequences (telomeres) that are erupted at each replication of the DNA. Their disappearance induces an arrest of the proliferation (G0).

In most tumor cells, there is a maintenance of telomeres during successive replications. This is due to the overexpression of telomerases, which are enzymes capable of adding repeated sequences at the end of chromosomes.


2. 1 - Data sheet of the cancer cell From a functional point of view, cancer cells are recognized for the common properties that differentiate them from normal cells:

1. independence from proliferation signals (growth factors) from the environment;

2. insensitivity to anti-proliferation signals; 3. resistance to apoptosis; 4. unlimited proliferation (loss of slavery); 5. ability to induce angiogenesis;

6. capacity for tissue invasion and metastatic spread. These functional anomalies are the result of a multi-step process in which the environment is not neutral. They are accompanied by morphological changes in the cell that most often allow to recognize its carcinogenic character by observing it under the light microscope.

However, two things must be said: â € ¢ none of these morphological abnormalities taken separately is specific to the

cancer cell (outside for some authors of abnormal mitosis figures); â € ¢ some tumors with authentically malignant behavior consist of cells

morphologically very close to their normal counterparts; other morphological criteria (bad limitation, vascular invasion) or evolutiv (metastases) are then necessary to assert malignancy.

2. 2 - Modifications of nucleus kernel in mitosis

â € ¢ Increased number of cells in mitosis. • Abnormal mitosis (Figure 8.4).

Interphasic nucleus â € ¢ Anisocaryosis (from Greek aniso = different and caryo = nucleus): unequal in size of a

kernel to each other. â € ¢ Increase in the nuclear-cytoplasmic ratio: most often due to a

increase in the size of the kernel. â € ¢ Hyperchromatism: dense and dark appearance of the nucleus related to condensation or

increase in the number of chromosomes (aneuploidy). â € ¢ Irregularities in shape and outlines (figures 8.5â € "8.8). â € ¢ Multinucleation (Figure 8.9).

Figure 8.4. Abnormal mitosis and an irregular nucleus cell

Figure 8.5. Abnormal mitosis, irregular hyperchromatic nuclei repelled by a voluminous cytoplasmic vacuole

Note the anisokaryosis: difference in size of the nuclei from one cell to another.

Figure 8.6. Cancer cells with hyperchromatic nuclei and increased nuclear-cytoplasmic ratio

Note the presence of two cells in apoptosis.

Figure 8.7. Binucleate cell with hyperchromatic nuclei, large nuclei and increased ocytoplasmic nuclear ratio

An abnormal mitosis. In the center: a cell in apoptosis.

Figure 8.8. Hyperchromatic nuclei with irregular contours

Figure 8.9. Monstrous cells of very large sizes with multiple irregular nuclei (glioblastoma: high-grade glial tumor)

Note the size of the nuclei of the normal glial tissue in comparison.

2. 3 - Changes in Cytoplasm Cytoskeleton

In the normal cell, the cytoskeleton consists of three types of filaments: 1. microtubules: structures of 20â € "25 nm of thickness consisting mainly of

tubulin polymers;

2. microfilaments: contractile structures of 6â € "8 nm in thickness containing in particular actin filaments;

3. Intermediate filaments: the most important are the cytoketine filaments (present in the epithelial and mesothelioma cells) and vimentin (especially in the connective cells = mesenchymal cells) .

In the cancer cell, the cytoskeleton is most often conserved, with distributional anomalies. It is not visible in light microscopy but its constituents can be evidenced by immunohistochemistry. This conservation is interesting for the pathologist because the demonstration of such or such types of intermediate filaments, for example, makes it possible to specify the tissue of origin of a cancer cell.

Seperate system â € ¢ Variations visible on standard stains, such as cytoplasmic vacuoles

(excess mucus) driving back the nucleus in mucosal adenocarcinomas, or a clear, optically empty cytoplasm (abnormal accumulation of glycogen) in clear cell kidney cancers, for example (Figures 8.10, 8.11).

â € ¢ Quantitative variations of normal secretions (eg peak monoclonal immunoglobulins in myeloma).

â € ¢ Appearance of new substances, either by depression of a synthesis of fetal proteins (ex: alpha fetoprotein, carcinoembryonic antigen = ACE) or by inappropriate secretion of a hormone (eg, ACTH secretion by some small cell carcinomas of the lung). These substances, considered as tumor markers, can be assayed in the blood when they are secreted or identified in situ by immunohistochemistry.

Figure 8.10. Clear cell adenocarcinoma of the kidney: the cytoplasm of the tumor cells are loaded with glycogen which gives them this clear aspect

Figure 8.11. Cytoplasmic vacuoles in the cytoplasm of a renal clear cell adenocarcinoma cell visible in electron microscopy

2. 4 - Membrane The membrane plays a crucial role in interactions between cells and interactions with the extracellular environment.

Morphological aspects

The morphological changes are visible only in electron microscopy: irregularities, microvilli, bubbles, projections, modifications of the junction systems. They are not taken into account for routine cancer diagnosis.

There are modifications of surface proteins, and especially adhesion molecules,

that are involved in intercellular interactions and extracellular cell-matrices.

To find out more: "Abnormalities of the adhesion molecules".

Functional aspects â € ¢ Membrane receptor abnormalities: increase in number and loss of

Result ©-regulation. â € ¢ Modifications of Membrane Enzymes: Increase of Protolytic Enzymes

(proteas, glycosidases) favoring the degradation of the intercellular substance. â € ¢ Modifications of membrane antigens:

o alteration or loss of normal antigens (Ag of species, organs or tissues);

o appearance of neoantigens: re-expression of embryonic antigens: alpha fetoprotein, carcinoembryonic antigen;

o abnormal expression of differentiation antigens, Ag associated with viruses (eg latent membrane protein of Epstein-Barr virus).

â € ¢ Modifications of the membrane permeability: o the increase in permeability for different cations (Ca ++ and Mg ++) plays

a role in several cellular functions, especially proliferation.


The tumor stroma is characterized by everything that is present within a tumor and is not a tumor cell. The stroma thus comprises the connective tissue, the vessels, the leucocytes and the extracellular matrix.

The stroma serves as a framework for the tumor and ensures its nutritional benefits. It is dependent on the tumor tissue whose cells can, for example, develop substances that will promote the growth of vessels. It is customary to reserve the term stroma for the connective tissue of malignant tumors and hardly to use it in the case of benign tumors, but nothing would be objectively opposed to it.

It is in invasive carcinomas that the stroma is most clearly individualized. There is, however, a stroma in all other solid tumors, consisting at least of the vessels and an extracellular matrix of variable abundance.

The morphological variations of the stroma are manifold, some of them are characteristic of a given tumor type and will therefore have a serological value for the diagnosis of the tumor type (Figure 8.12).

Figure 8.12. Tumor Stroma

3. 1 - Quantitative variations

Some very different carcinomas have a stroma that may be exactly proportioned to epithelial proliferation. In endocrine tumors, the stroma often has sinusoidal capillaries similar to those of a normal endocrine gland (adaptive stroma).

More often, the stroma is disproportionate to epithelial proliferation: â € ¢ when it is relatively scarce, the tumor will be soft, often necrotic,

similar macroscopically to ceral tissue. It is a cancer that we will macroscopically characterize as "encampoloid";

â € ¢ Conversely, when it is very abundant, rich in collagen fibers, the tumor will be hard and retracted, it is the squirrh. This reduction, comparable to that of certain pathological scars, is related to the presence of numerous myofibroblasts.

3. 2 - Qualitative variations The connective tissue of the stroma possesses certain retactile properties of normal connective tissue. It can produce an inflammatory reaction. This will occur, for example, during the destruction of the tumor tissue by irradiation. The necrosis of the tumor cells triggers an exudative reaction. It may even occur with a foreign body reaction around keratinous scales developed by the tumor. In some tumors, the inflammatory reaction of the stroma is a tuberculous reaction.

Some tumors have a stroma rich in lymphocyte or plasmocytic cells, which may be the manifestation of an immune response. This aspect sometimes goes hand in hand with a better prognosis.


The neovascularization resulting from tumor angiogenesis presents a state of maximum cellular activation for mediocre perfusion efficiency. It is very heterogeneous in density, by its phenotypic maturation from one tumor zone to another and from one tumor to the other.

A tumor can not grow beyond 1 to 2 mm without the help of a rich blood supply. The relationships between the tumor tissue itself and its vascularity are therefore critical in the natural history of each cancer.

Vasculogenesis is a vascular proliferation due to the differentiation of precursor cells, common to blood lines, into endothelial cells that spread, associate and establish Vascular network. This term is very predominantly reserved for the corresponding stages of embryogenesis.

Angiogenesis is a vascular proliferation caused by vascular budding from pre-existing vessels, then the installation of a network and its differentiation into different functional areas. This process involves the recruitment and differentiation of perioperative cells and smooth muscle cells, which help to stabilize the new network and give it functional efficacy. Angiogenesis is often related to inflammatory or tumor processes.

4. 1 - Tumor Peripheral Vascularization In the peripheral zone of tumor invasion, the proliferation of endothelial cells is active and it produces new vessels that are often abnormal. La prolifération vasculaire est particulièrement vigoureuse et l’index de prolifération des cellules endothéliales est 50 à 200 fois plus élevé que pour les mêmes cellules des tissus normaux.

Les vaisseaux créés au sein de la tumeur sont anormaux. Ce sont des canaux à paroi mince plutôt de type veinulaire, irrégulièrement anastomosés avec de nombreux culs-de-sac. they have

tendance à former des shunts artério-veineux. La bordure endothéliale est incomplète (sauf dans les tumeurs cérébrales primitives), la membrane basale est souvent absente, les cellules satellites (péricytes et cellules musculaires lisses) raréfiées. Il n’y a pas d’innervation et de nombreux espaces vasculaires sont bordés directement par les cellules tumorales.

Ces vaisseaux défectifs ne sont pas contrôlables par les mécanismes locaux habituels (mécanisme nerveux et système des cytokines). L’efficacité de perfusion est médiocre. Les courts-circuits artério-veineux s’opposent à une perfusion capillaire efficace. Le régime liquidien est chaotique avec des inversions de flux et une stase selon une période de 2–3 min.

Le drainage des fluides interstitiels est déficient en liaison avec l’excès de perméabilité et l’absence de drainage lymphatique fonctionnel.

Enfin, cette vascularisation est très inégalement répartie en densité d’un point à un autre de la tumeur.

Dans cette région de la tumeur on retrouve des taux élevés de facteur de croissance endothélial vasculaire (VEGF), du facteur de croissance fibroblastique basique (FGFb), de la phosphorylase de la thymidine (TP). Tous ces facteurs sont induits par l’hypoxie.

4. 2 - Vascularisation au centre des tumeurs Au fil de la croissance tumorale, les marges s’incorporent dans le centre de la tumeur, mêlant néovascularisation et vascularisation d’origine de l’hôte. La densité de microcirculation devient 4 à 10 fois plus faible qu’au niveau des berges. Les cellules tumorales s’adaptent à l’hypoxie en activant la glycolyse anaérobie. Les cellules endothéliales activent la fabrication des molécules du stress hypoxique (VEGF, TP, complexe VEGF/récepteur du VEGF) et les inhibiteurs de l’apoptose (bcl-2). Quand le mécanisme anti-apoptotique endothélial défaille, les cellules tumorales sont en situation d’accès facile au compartiment intravasculaire.


La réponse immune joue un rôle majeur dans la défense de l’organisme contre les tumeurs, et est probablement responsable du contrôle et de la majorité des tumeurs. Ceci est notamment valable à la phase initiale d’émergence des tumeurs, mais l’infiltration tumorale par des lymphocytes à un stade plus évolué reste un facteur pronostic important pour plusieurs tumeurs.

5. 1 - Effecteurs de la réponse immune anti-tumorale La réponse immune anti-tumorale fait intervenir :

• l’immunité innée, avec notamment des cellules cytotoxiques (ex : lymphocytes NK), et des facteurs solubles (ex : interféron gamma), qui peuvent avoir des effets directs ou indirects (pro-inflammatoire ou anti-angiogénique) ;

• l’immunité adaptative, c’est-à -dire dépendante de la reconnaissance de molécules spécifiques produites par la tumeur.

Les mécanismes effecteurs de la réponse immune anti-tumorale sont : • la cytotoxicité directe par les lymphocytes NK (NK = natural killer), les lymphocytes

T cytotoxiques (CD8), ou les cellules dendritiques IKDC (Interferon gamma producing killer dendritic cells) (tableau 8.4) ;

• la cytotoxicité médiée par les anticorps, qui paraît notamment très utile en thérapeutique, avec l’utilisation d’Ac monoclonaux spécifiques de certains antigènes exprimés par les tumeurs (CD20, EGFR) ;

• la production de facteurs solubles capables de moduler la réponse inflammatoire locale et/ou l’angiogénèse, tels l’interféron gamma.

Tableau 84 : Mécanismes effecteurs de la réponse immunitaire anti-tumorale par cytotoxicité directe

5. 2 - Échappement des tumeurs à la réponse immune Les mécanismes d’échappement des tumeurs concernent à la fois la réponse immune innée et adaptative. Il peut s’agir :

• d’une immuno-sélection : sélection au cours du temps des sous-clones tumoraux ayant acquis des mécanismes d’échappement à la réponse immune. Ces sous-clones sont généralement sélectionnés en raison de la diminution de l’expression de cibles ou l’augmentation de l’expression d’inhibiteurs ;

• d’une immuno-subversion (induction d’une tolérance spécifique) mettant en jeu des phénomènes plus complexes de coopération intercellulaire.

En savoir plus : « Exemples de mécanismes impliqués dans l’immuno-sélection ».

5. 3 - Stratégies thérapeutiques immunologiques Pour les tumeurs viro-induites la stratégie vaccinale peut être efficace. Ainsi la vaccination d’une population contre l’hépatite B permet de prévenir la survenue d’hépatites chroniques B et de réduire de façon importante l’incidence du carcinome hépatocellulaire qu’elle aurait induit.

L’immunothérapie par instillation du vaccin BCG en intravésical est utilisée depuis de nombreuses années pour contrôler l’évolution des tumeurs superficielles de vessie de haut grade.

Des injections d’interleukine 2 peuvent induire des régressions métastatiques dans certains cancers du rein ou dans les mélanomes.

Actuellement, plusieurs anticorps monoclonaux sont dirigés contre des antigènes spécifiques des tumeurs. Ces Ac sont éventuellement associés à des radio-éléments ou des toxines.

En savoir plus : « Exemples d'anticorps monoclonaux anti-tumoraux ».